A Study to Investigate Safety, Tolerability, and PK of Or... | NCT05437419

NCT05437419

Status Module

Sponsor/Collaborators Module

Name	Class
Parexel	INDUSTRY

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Cohort 1	Experimental	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).	Drug: TCK-276 Drug: TCK-276 Placebo
Cohort 2	Experimental	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).	Drug: TCK-276 Drug: TCK-276 Placebo
Cohort 3	Experimental	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).	Drug: TCK-276 Drug: TCK-276 Placebo
Cohort 4	Experimental	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).	Drug: TCK-276 Drug: TCK-276 Placebo

Name	Type	Description	Arm Group Labels	Other Names
TCK-276	Drug	Patients will receive an oral dose of TCK-276 QD under fed conditions from Day 1 to Day 7.	Cohort 1 Cohort 2 Cohort 3 Cohort 4

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Number ot Participants With Treatment Emergent Adverse Events	To evaluate the safety and tolerability of multiple oral doses of TCK-276 or placebo in patients with rheumatoid arthritis (RA)	42 days (duration of study)

Secondary Outcomes

Measure	Description	Time Frame
Cmax: Plasma Concentrations of TCK-276 and TEI-W00595 (Metabolite)	Cmax: Plasma Concentrations of TCK-276 and TEI-W00595 with time-concentration profile	Day 1 and Day 7
Tmax: Time of Maximum Plasma Concentration Determined Directly From the Concentration-time Profile

Eligibility Module

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:
1. 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.
2. 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.
Permitted medications include: anti-malarials; nonsteroidal anti-inflammatory drugs including selective cyclooxygenase-2 inhibitors at approved dosage, and low dose oral corticosteroids; methotrexate concomitantly with folic acid or folinic acid.

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.
Patient has positive test for hepatitis B surface antigen (HBsAg), anti-hepatitis B core (HBc) antibodies, hepatitis C virus (HCV) antibody, and/or human immunodeficiency virus (HIV) antibody at Screening Visit.
Patient has QT interval corrected for heart rate (QTc) using Fridericia's correction (QTcF) > 450 ms for males or QTcF > 470 ms for females either at the Screening Visit or Admission, based on safety 12-lead electrocardiogram (ECG). Patient has Screening or Admission ECG with second- or third-degree atrioventricular block, bundle branch block, arrhythmia (but not sinus arrhythmia or supraventricular premature beats), or illegible QT interval.
Patient has history or evidence of cardiopathy, acute coronary syndrome, hypertrophic cardiomyopathy, myocarditis or QT prolongation syndrome.
Patient is unwilling to abstain from drinks and foods containing alcohol, grapefruit, or caffeine
Patient has donated blood or experienced acute blood loss (including plasmapheresis) of greater than 500 mL within 90 days prior to the first dose of study drug.
Patients with a known immunodeficiency disorder. Have a history of a major organ transplant or hematopoietic stem cell/marrow transplant.
Patients with infections requiring treatment or hospitalization within 14 days prior to the Screening Visit, parenteral antimicrobial therapy within 60 days prior to the Screening Visit, infected joint prosthesis; history of herpes zoster, active herpes simplex, or herpes simplex on suppressive therapy.
Patient has a chronic hepatic disease or hepatic impairment.
Patient has a history of Mycobacterium tuberculosis or positive interferon gamma release assay for tuberculosis (IGRA-TB) or abnormal chest X-ray (for positive IGRA-TB patients).
Patient has a history of any lymphoproliferative disorder.
Patient has a history of COVID-19 unless fully recovered with no sequelae for 14 days.
Patient who had a severe course of COVID-19 (extracorporeal membrane oxygenation, mechanically ventilated).
Patient who has recent exposure to someone who has COVID-19 symptoms or positive test result.
Patient who has a positive reverse transcription polymerase chain reaction (RT-PCR) test for Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2).
Patient who has clinical signs and symptoms consistent with SARS-CoV-2 infection.
Patients may not receive any live/attenuated vaccine from 30 days prior to the Screening Visit until Day 14 Follow-up Visit.
COVID-19 vaccine should not be given 1 week prior to the Screening Visit.
Patients with malignancy or history of malignancy except adequately treated or excised non-metastatic basal cell or squamous cell cancer of the skin or cervical carcinoma in situ. Previous treatment with total lymphoid irradiation.
History of recurrent inflammatory joint disease other than RA or history of any other autoimmune rheumatic diseases other than Sjogren's syndrome.
Major surgery within 30 days prior to the Screening Visit or patients with planned surgery.
Patients who have an abnormal chest X-ray for interstitial lung disease (ILD) and/or patients with history of ILD.
History of fainting or family history of sudden death.
Patient has any disorder that would interfere with the absorption, distribution, metabolism or excretion of study drug.
Patient has a history of deep vein thrombosis and/or pulmonary embolism.
Patient has poor venous access.

Contacts/Locations Module

Name	Affiliation	Role
Tatyana Zubkovskaya	Medical Director	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Orange County Research Center		Tustin	California	92780	United States
St. Jude Clinical Research, LLC

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
39002122	Derived	Tasaki D, Tsuruda K, Sun S, Tsumura Y, Asano S, Suzuki Y, Tsujimoto S, Miura D, Sato H. A double-blind, placebo-controlled, randomized multiple dose phase 1b trial of a CDK4/6 inhibitor, TCK-276, in patients with active rheumatoid arthritis. Rheumatology (Oxford). 2025 Mar 1;64(3):1036-1044. doi: 10.1093/rheumatology/keae357.

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Cohort 1	The patient will receive 10 mg of TCK-276 orally from Day 1 to Day 7 (once daily (QD) under fed conditions).
FG001	Cohort 2	The patient will receive 25 mg of TCK-276 orally from Day 1 to Day 7 (once daily (QD) under fed conditions).

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Dec 12, 2022	Jun 3, 2024

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

No data available

No data is available for this block.

Masking Info

Type of Units Analyzed

Arm/Group Information

ID	Title	Description
BG000	Cohort 1	The patient will receive 10 mg of TCK-276 orally from Day 1 to Day 7 (once daily (QD) under fed conditions).
BG001	Cohort 2	The patient will receive 25 mg of TCK-276 orally from Day 1 to Day 7 (once daily (QD) under fed conditions).
BG002	Cohort 3	The patient will receive 75 mg of TCK-276 orally from Day 1 to Day 7 (once daily (QD) under fed conditions).
BG003	Cohort 4	The patient will receive 175 mg of TCK-276 orally from Day 1 to Day 7 (once daily (QD) under fed conditions).
BG004	Pooled Placebo Group	The patient will receive matching placebo orally from Day 1 to Day 7 (once daily (QD) under fed conditions).
BG005	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Categorical

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
<=18 years	BG0000 BG0010 BG0020 BG003

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG0006 BG0016 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG0005 BG0015 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000 BG0010 BG002

Region of Enrollment

Number

participants

Title

Denominators

Categories

United States

Title	Measurements
	BG0006 BG0016 BG002

Height

Mean

Standard Deviation

Title

Denominators

Categories

Title	Measurements
	BG000163.5± 3.6472 BG001163.03± 5.8745 BG002

Weight

Mean

Standard Deviation

Title

Denominators

Categories

Title	Measurements
	BG00074.950± 7.5688 BG00173.252± 6.6383 BG002

BMI

Mean

Standard Deviation

kg/m2

Title

Denominators

Categories

Title	Measurements
	BG00028.035± 2.5991 BG00127.605± 2.6567 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Number ot Participants With Treatment Emergent Adverse Events

To evaluate the safety and tolerability of multiple oral doses of TCK-276 or placebo in patients with rheumatoid arthritis (RA)

Posted

Number

participants

42 days (duration of study)

ID	Title	Description
OG000	Cohort 1	The patient will receive 10 mg of TCK-276 orally from Day 1 to Day 7 (once daily (QD) under fed conditions).
OG001	Cohort 2	The patient will receive 25 mg of TCK-276 orally from Day 1 to Day 7 (once daily (QD) under fed conditions).
OG002	Cohort 3	The patient will receive 75 mg of TCK-276 orally from Day 1 to Day 7 (once daily (QD) under fed conditions). .
OG003	Cohort 4	The patient will receive 175 mg of TCK-276 orally from Day 1 to Day 7 (once daily (QD) under fed conditions).
OG004	Pooled Placebo Group	The patient will receive matching placebo for TCK-276 orally from Day 1 to Day 7 (once daily (QD) under fed conditions).

Units	Counts
Participants	OG0006 OG0016 OG0026 OG003

Title

Denominators

Categories

Title	Measurements
	OG0002 OG0012 OG0022 OG003

Secondary

Cmax: Plasma Concentrations of TCK-276 and TEI-W00595 (Metabolite)

Cmax: Plasma Concentrations of TCK-276 and TEI-W00595 with time-concentration profile

One subject each from Cohorts 1 and 3 was excluded due to the occurrence of an event that met the definition of exclusion from the PK analysis.

Posted

Mean

Standard Deviation

ng/mL

Day 1 and Day 7

ID	Title	Description
OG000	Cohort 1	The patient will receive 10 mg of TCK-276 orally from Day 1 to Day 7 (once daily (QD) under fed conditions).
OG001	Cohort 2	The patient will receive 25 mg of TCK-276 orally from Day 1 to Day 7 (once daily (QD) under fed conditions).
OG002	Cohort 3	The patient will receive 75 mg of TCK-276 orally from Day 1 to Day 7 (once daily (QD) under fed conditions). .
OG003	Cohort 4	The patient will receive 175 mg of TCK-276 orally from Day 1 to Day 7 (once daily (QD) under fed conditions).

Secondary

Tmax: Time of Maximum Plasma Concentration Determined Directly From the Concentration-time Profile

To evaluate tmax as pharmacokinetic (PK) variables of TCK-276 and its metabolite in patients with RA after multiple ascending dose (MAD) administration

One subject each from Cohorts 1 and 3 was excluded due to the occurrence of an event that met the definition of exclusion from the PK analysis.

Posted

Median

Full Range

Day 1 and Day 7

ID	Title	Description
OG000	Cohort 1	The patient will receive 10 mg of TCK-276 orally from Day 1 to Day 7 (once daily (QD) under fed conditions).
OG001	Cohort 2	The patient will receive 25 mg of TCK-276 orally from Day 1 to Day 7 (once daily (QD) under fed conditions).
OG002	Cohort 3	The patient will receive 75 mg of TCK-276 orally from Day 1 to Day 7 (once daily (QD) under fed conditions). .
OG003	Cohort 4	The patient will receive 175 mg of TCK-276 orally from Day 1 to Day 7 (once daily (QD) under fed conditions).

Secondary

t½: Terminal Elimination Half-life

To evaluate t½ as PK variables of TCK-276 and its metabolite in patients with RA after multiple ascending dose (MAD) administration

One subject each from Cohorts 1 and 3 was excluded due to the occurrence of an event that met the definition of exclusion from the PK analysis.

Posted

Mean

Standard Deviation

Day 1 and Day 7

ID	Title	Description
OG000	Cohort 1	The patient will receive 10 mg of TCK-276 orally from Day 1 to Day 7 (once daily (QD) under fed conditions).
OG001	Cohort 2	The patient will receive 25 mg of TCK-276 orally from Day 1 to Day 7 (once daily (QD) under fed conditions).
OG002	Cohort 3	The patient will receive 75 mg of TCK-276 orally from Day 1 to Day 7 (once daily (QD) under fed conditions). .
OG003	Cohort 4	The patient will receive 175 mg of TCK-276 orally from Day 1 to Day 7 (once daily (QD) under fed conditions).

Secondary

AUCtau: Area Under the Plasma Concentration-time Curve Over a Dosing Interval, Tau = 24 Hours

To evaluate AUCtau as PK variables of TCK-276 and its metabolite in patients with RA after multiple ascending dose (MAD) administration

One subject each from Cohorts 1 and 3 was excluded due to the occurrence of an event that met the definition of exclusion from the PK analysis.

Posted

Mean

Standard Deviation

h*ng/mL

Day 1 and Day 7

ID	Title	Description
OG000	Cohort 1	The patient will receive 10 mg of TCK-276 orally from Day 1 to Day 7 (once daily (QD) under fed conditions).
OG001	Cohort 2	The patient will receive 25 mg of TCK-276 orally from Day 1 to Day 7 (once daily (QD) under fed conditions).
OG002	Cohort 3	The patient will receive 75 mg of TCK-276 orally from Day 1 to Day 7 (once daily (QD) under fed conditions). .
OG003	Cohort 4	The patient will receive 175 mg of TCK-276 orally from Day 1 to Day 7 (once daily (QD) under fed conditions).

Secondary

AUC0-inf: Area Under the Plasma Concentration Time Curve From Pre-dose (Time 0) Extrapolated to Infinite Time

AUC0-inf:Area under the plasma concentration time curve from pre-dose (time 0) extrapolated to infinite time (Days 1 and 7)

One subject each from Cohorts 1 and 3 was excluded due to the occurrence of an event that met the definition of exclusion from the PK analysis.

Posted

Mean

Standard Deviation

h*ng/mL

Day 1 and Day 7

ID	Title	Description
OG000	Cohort 1	The patient will receive 10 mg of TCK-276 orally from Day 1 to Day 7 (once daily (QD) under fed conditions).
OG001	Cohort 2	The patient will receive 25 mg of TCK-276 orally from Day 1 to Day 7 (once daily (QD) under fed conditions).
OG002	Cohort 3	The patient will receive 75 mg of TCK-276 orally from Day 1 to Day 7 (once daily (QD) under fed conditions). .
OG003	Cohort 4	The patient will receive 175 mg of TCK-276 orally from Day 1 to Day 7 (once daily (QD) under fed conditions).

Secondary

Clearance (CL)/F: Apparent Total Body Clearance (Parent Only)

To evaluate CL/F as PK variables of TCK-276 in patients with RA after multiple ascending dose (MAD) administration

One subject each from Cohorts 1 and 3 was excluded due to the occurrence of an event that met the definition of exclusion from the PK analysis.

Posted

Mean

Standard Deviation

L/h

Day 1 and Day 7

ID	Title	Description
OG000	Cohort 1	The patient will receive 10 mg of TCK-276 orally from Day 1 to Day 7 (once daily (QD) under fed conditions).
OG001	Cohort 2	The patient will receive 25 mg of TCK-276 orally from Day 1 to Day 7 (once daily (QD) under fed conditions).
OG002	Cohort 3	The patient will receive 75 mg of TCK-276 orally from Day 1 to Day 7 (once daily (QD) under fed conditions). .
OG003	Cohort 4	The patient will receive 175 mg of TCK-276 orally from Day 1 to Day 7 (once daily (QD) under fed conditions).

Secondary

Vz/F: Apparent Volume of Distribution Based on Terminal Phase (Parent Only)

To evaluate Vz/F as PK variables of TCK-276 in patients with RA after multiple ascending dose (MAD) administration

One subject each from Cohorts 1 and 3 was excluded due to the occurrence of an event that met the definition of exclusion from the PK analysis.

Posted

Mean

Standard Deviation

Day 1 and Day 7

ID	Title	Description
OG000	Cohort 1	The patient will receive 10 mg of TCK-276 orally from Day 1 to Day 7 (once daily (QD) under fed conditions).
OG001	Cohort 2	The patient will receive 25 mg of TCK-276 orally from Day 1 to Day 7 (once daily (QD) under fed conditions).
OG002	Cohort 3	The patient will receive 75 mg of TCK-276 orally from Day 1 to Day 7 (once daily (QD) under fed conditions). .
OG003	Cohort 4	The patient will receive 175 mg of TCK-276 orally from Day 1 to Day 7 (once daily (QD) under fed conditions).

Secondary

MRT0-inf: Mean Residence Time Extrapolated to Infinity

To evaluate MRT0-inf as PK variables of TCK-276 and its metabolite in patients with RA after multiple ascending dose (MAD) administration

One subject each from Cohorts 1 and 3 was excluded due to the occurrence of an event that met the definition of exclusion from the PK analysis.

Posted

Mean

Standard Deviation

Day 1 and Day 7

ID	Title	Description
OG000	Cohort 1	The patient will receive 10 mg of TCK-276 orally from Day 1 to Day 7 (once daily (QD) under fed conditions).
OG001	Cohort 2	The patient will receive 25 mg of TCK-276 orally from Day 1 to Day 7 (once daily (QD) under fed conditions).
OG002	Cohort 3	The patient will receive 75 mg of TCK-276 orally from Day 1 to Day 7 (once daily (QD) under fed conditions). .
OG003	Cohort 4	The patient will receive 175 mg of TCK-276 orally from Day 1 to Day 7 (once daily (QD) under fed conditions).

Secondary

Racc (Cmax): Accumulation Ratio Based on Cmax

Racc (Cmax) calculated as Cmax on Day 7/Cmax on Day 1.

One subject each from Cohorts 1 and 3 was excluded due to the occurrence of an event that met the definition of exclusion from the PK analysis.

Posted

Mean

Standard Deviation

Ratio

Day 1 and Day 7

ID	Title	Description
OG000	Cohort 1	The patient will receive 10 mg of TCK-276 orally from Day 1 to Day 7 (once daily (QD) under fed conditions).
OG001	Cohort 2	The patient will receive 25 mg of TCK-276 orally from Day 1 to Day 7 (once daily (QD) under fed conditions).
OG002	Cohort 3	The patient will receive 75 mg of TCK-276 orally from Day 1 to Day 7 (once daily (QD) under fed conditions). .
OG003	Cohort 4	The patient will receive 175 mg of TCK-276 orally from Day 1 to Day 7 (once daily (QD) under fed conditions).

Secondary

Racc (AUCtau): Accumulation Ratio Based on AUCtau

Racc (AUCtau) calculated as AUCtau on Day 7/AUCtau on Day 1. To evaluate Racc (AUCtau) as PK variables of TCK-276 and its metabolite in patients with RA after multiple ascending dose (MAD) administration

One subject each from Cohorts 1 and 3 was excluded due to the occurrence of an event that met the definition of exclusion from the PK analysis.

Posted

Mean

Standard Deviation

Ratio

Day 1 and Day 7

ID	Title	Description
OG000	Cohort 1	The patient will receive 10 mg of TCK-276 orally from Day 1 to Day 7 (once daily (QD) under fed conditions).
OG001	Cohort 2	The patient will receive 25 mg of TCK-276 orally from Day 1 to Day 7 (once daily (QD) under fed conditions).
OG002	Cohort 3	The patient will receive 75 mg of TCK-276 orally from Day 1 to Day 7 (once daily (QD) under fed conditions). .
OG003	Cohort 4	The patient will receive 175 mg of TCK-276 orally from Day 1 to Day 7 (once daily (QD) under fed conditions).

Secondary

Metabolic Ratio (MR) for Cmax

Molar metabolic ratio of Cmax calculated as (Cmax [metabolite] × molecular weight of parent)/(Cmax [parent] × molecular weight of metabolite).

One subject each from Cohorts 1 and 3 was excluded due to the occurrence of an event that met the definition of exclusion from the PK analysis.

Posted

Mean

Standard Deviation

Ratio

Day 1 and Day 7

ID	Title	Description
OG000	Cohort 1	The patient will receive 10 mg of TCK-276 orally from Day 1 to Day 7 (once daily (QD) under fed conditions).
OG001	Cohort 2	The patient will receive 25 mg of TCK-276 orally from Day 1 to Day 7 (once daily (QD) under fed conditions).
OG002	Cohort 3	The patient will receive 75 mg of TCK-276 orally from Day 1 to Day 7 (once daily (QD) under fed conditions). .
OG003	Cohort 4	The patient will receive 175 mg of TCK-276 orally from Day 1 to Day 7 (once daily (QD) under fed conditions).

Secondary

MR for Area Under the Plasma Concentration-time Curve (AUC)Tau

Molar metabolic ratio of AUC calculated as (AUC [metabolite] × molecular weight of parent)/(AUC [parent] × molecular weight of metabolite). To evaluate MR AUC as PK variables of TCK-276 and its metabolite in patients with RA after multiple ascending dose (MAD) administration

One subject each from Cohorts 1 and 3 was excluded due to the occurrence of an event that met the definition of exclusion from the PK analysis.

Posted

Mean

Standard Deviation

Ratio

Day 1 and Day 7

ID	Title	Description
OG000	Cohort 1	The patient will receive 10 mg of TCK-276 orally from Day 1 to Day 7 (once daily (QD) under fed conditions).
OG001	Cohort 2	The patient will receive 25 mg of TCK-276 orally from Day 1 to Day 7 (once daily (QD) under fed conditions).
OG002	Cohort 3	The patient will receive 75 mg of TCK-276 orally from Day 1 to Day 7 (once daily (QD) under fed conditions). .
OG003	Cohort 4

Secondary

MR for Area Under the Plasma Concentration-time Curve (AUC)0-inf

Molar metabolic ratio of AUC calculated as (AUC [metabolite] × molecular weight of parent)/(AUC [parent] × molecular weight of metabolite) 0-inf. To evaluate MR AUC 0-inf as PK variables of TCK-276 and its metabolite in patients with RA after multiple ascending dose (MAD) administration

One subject each from Cohorts 1 and 3 was excluded due to the occurrence of an event that met the definition of exclusion from the PK analysis.

Posted

Mean

Standard Deviation

Ratio

Day 1 and Day 7

ID	Title	Description
OG000	Cohort 1	The patient will receive 10 mg of TCK-276 orally from Day 1 to Day 7 (once daily (QD) under fed conditions).
OG001	Cohort 2	The patient will receive 25 mg of TCK-276 orally from Day 1 to Day 7 (once daily (QD) under fed conditions).
OG002	Cohort 3	The patient will receive 75 mg of TCK-276 orally from Day 1 to Day 7 (once daily (QD) under fed conditions). .
OG003	Cohort 4

Secondary

Ae 0-24: Amount of Study Drug Excreted Unchanged in the Urine (Days 1 and 7)

Ae 0-24: Amount of study drug excreted unchanged in the urine (Days 1 and 7) over 24 hours

One subject each from Cohorts 1 and 3 was excluded due to the occurrence of an event that met the definition of exclusion from the PK analysis.

Posted

Mean

Standard Deviation

Day 1 and Day 7

ID	Title	Description
OG000	Cohort 1	The patient will receive 10 mg of TCK-276 orally from Day 1 to Day 7 (once daily (QD) under fed conditions).
OG001	Cohort 2	The patient will receive 25 mg of TCK-276 orally from Day 1 to Day 7 (once daily (QD) under fed conditions).
OG002	Cohort 3	The patient will receive 75 mg of TCK-276 orally from Day 1 to Day 7 (once daily (QD) under fed conditions). .
OG003	Cohort 4	The patient will receive 175 mg of TCK-276 orally from Day 1 to Day 7 (once daily (QD) under fed conditions).

Secondary

Fe 0-24: Percentage of Study Drug Excreted Unchanged in the Urine (Days 1 and 7)

Fe 0-24: Percentage of study drug excreted unchanged in the urine (Days 1 and 7) over 24 hours

One subject each from Cohorts 1 and 3 was excluded due to the occurrence of an event that met the definition of exclusion from the PK analysis.

Posted

Mean

Standard Deviation

percentage of drug

Day 1 and Day 7

ID	Title	Description
OG000	Cohort 1	The patient will receive 10 mg of TCK-276 orally from Day 1 to Day 7 (once daily (QD) under fed conditions).
OG001	Cohort 2	The patient will receive 25 mg of TCK-276 orally from Day 1 to Day 7 (once daily (QD) under fed conditions).
OG002	Cohort 3	The patient will receive 75 mg of TCK-276 orally from Day 1 to Day 7 (once daily (QD) under fed conditions). .
OG003	Cohort 4	The patient will receive 175 mg of TCK-276 orally from Day 1 to Day 7 (once daily (QD) under fed conditions).

Secondary

Clearance Renal (CLr): Renal Clearance (Days 1 and 7)

CLr: Renal clearance Day 1 and Day 7 (24 hours)

One subject each from Cohorts 1 and 3 was excluded due to the occurrence of an event that met the definition of exclusion from the PK analysis.

Posted

Mean

Standard Deviation

L/h

Day 1 and Day 7

ID	Title	Description
OG000	Cohort 1	The patient will receive 10 mg of TCK-276 orally from Day 1 to Day 7 (once daily (QD) under fed conditions).
OG001	Cohort 2	The patient will receive 25 mg of TCK-276 orally from Day 1 to Day 7 (once daily (QD) under fed conditions).
OG002	Cohort 3	The patient will receive 75 mg of TCK-276 orally from Day 1 to Day 7 (once daily (QD) under fed conditions). .
OG003	Cohort 4	The patient will receive 175 mg of TCK-276 orally from Day 1 to Day 7 (once daily (QD) under fed conditions).

Secondary

Ae 0-72: Amount of Study Drug Excreted Unchanged in the Urine (Day 7)

Ae 0-72: Amount of study drug excreted unchanged in the urine (Day 7) over a 72 hour period

One subject each from Cohorts 1 and 3 was excluded due to the occurrence of an event that met the definition of exclusion from the PK analysis.

Posted

Mean

Standard Deviation

Day 7 0-72 hours

ID	Title	Description
OG000	Cohort 1	The patient will receive 10 mg of TCK-276 orally from Day 1 to Day 7 (once daily (QD) under fed conditions).
OG001	Cohort 2	The patient will receive 25 mg of TCK-276 orally from Day 1 to Day 7 (once daily (QD) under fed conditions).
OG002	Cohort 3	The patient will receive 75 mg of TCK-276 orally from Day 1 to Day 7 (once daily (QD) under fed conditions). .
OG003	Cohort 4	The patient will receive 175 mg of TCK-276 orally from Day 1 to Day 7 (once daily (QD) under fed conditions).

Secondary

Fe 0-72: Percentage of Study Drug Excreted Unchanged in the Urine

Fe 0-72: Percentage of study drug excreted unchanged in the urine on Day 7 (72 hours)

One subject each from Cohorts 1 and 3 was excluded due to the occurrence of an event that met the definition of exclusion from the PK analysis.

Posted

Mean

Standard Deviation

percentage of drug

Day 7 0-72 hours

ID	Title	Description
OG000	Cohort 1	The patient will receive 10 mg of TCK-276 orally from Day 1 to Day 7 (once daily (QD) under fed conditions).
OG001	Cohort 2	The patient will receive 25 mg of TCK-276 orally from Day 1 to Day 7 (once daily (QD) under fed conditions).
OG002	Cohort 3	The patient will receive 75 mg of TCK-276 orally from Day 1 to Day 7 (once daily (QD) under fed conditions). .
OG003	Cohort 4	The patient will receive 175 mg of TCK-276 orally from Day 1 to Day 7 (once daily (QD) under fed conditions).

Arm/Groups

ID	Title	Description	Deaths (At Risk)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Cohort 1	The patient will receive 10 mg of TCK-276 orally from Day 1 to Day 7 (once daily (QD) under fed conditions).	6	6	2	6
EG001	Cohort 2	The patient will receive 25 mg of TCK-276 orally from Day 1 to Day 7 (once daily (QD) under fed conditions).	6	6	2	6
EG002	Cohort 3	The patient will receive 75 mg of TCK-276 orally from Day 1 to Day 7 (once daily (QD) under fed conditions). .	6	6	2	6
EG003	Cohort 4	The patient will receive 175 mg of TCK-276 orally from Day 1 to Day 7 (once daily (QD) under fed conditions).	6	6	1	6
EG004	Pooled Placebo Group	The patient will receive matching placebo for TCK-276 orally from Day 1 to Day 7 (once daily (QD) under fed conditions).	8	8	2	8

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Sinus Tachycardia	Cardiac disorders	MedDRA version 25.0	Systematic Assessment	EG0002 events1 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected6 at risk EG0030 events0 affected6 at risk EG0040 events0 affected8 at risk
Tachycardia	Cardiac disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected6 at risk EG0020 events0 affected6 at risk EG003
Ventricular extrasystoles	Cardiac disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected6 at risk EG0020 events0 affected6 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0021 events1 affected6 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected6 at risk EG003
C-reactive protein increased	Investigations	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected6 at risk EG003
Electrocardiogram T wave abnormal	Investigations	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0021 events1 affected6 at risk EG003
Headache	Nervous system disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0021 events1 affected6 at risk EG003
Presyncope	Nervous system disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected6 at risk EG0020 events0 affected6 at risk EG003
Anemia	Blood and lymphatic system disorders	MedDRA version 25.0	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected6 at risk EG003
Ocular hyperaemia	Eye disorders	MedDRA version 25.0	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected6 at risk EG003
Ulcerative keratitis	Eye disorders	MedDRA version 25.0	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected6 at risk EG003
COVID-19	Infections and infestations	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected6 at risk EG003
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA version 25.0	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected6 at risk EG003

ID	Term
D001172	Arthritis, Rheumatoid
D001327	Autoimmune Diseases

Ancestor Terms

ID	Term
D001168	Arthritis
D007592	Joint Diseases
D009140	Musculoskeletal Diseases
D012216	Rheumatic Diseases
D003240	Connective Tissue Diseases
D017437	Skin and Connective Tissue Diseases
D007154	Immune System Diseases

BG003165.533± 11.6610

BG004164.878± 5.2737

BG005163.515± 6.800

BG00380.678± 9.3768

BG00473.829± 4.5924

BG00575.454± 6.8510

BG00329.438± 1.5542

BG00427.219± 2.2859

BG00528.247± 2.2170

Units	Counts
Participants	OG0005 OG0016 OG0025 OG0036

The patient will receive 175 mg of TCK-276 orally from Day 1 to Day 7 (once daily (QD) under fed conditions).

Units	Counts
Participants	OG0005 OG0016 OG0025 OG0036

EG0040 events0 affected8 at risk

EG0041 events1 affected8 at risk

EG0040 events0 affected8 at risk

EG0041 events1 affected8 at risk

EG0040 events0 affected8 at risk

Title	Measurements
	OG00013.6± 5.46 OG00111.4± 6.15 OG00213.6± 7.73 OG00311.0± 4.39

Title	Measurements
	OG0004.78± 0.716 OG0015.15± 1.60 OG0025.53± 1.27 OG0035.49± 1.28

Title	Measurements
	OG0009.10± 5.73 OG00110.7± 6.42 OG00212.8± 5.28 OG00311.7± 4.69

Title	Measurements
	OG000172± 32.8 OG001363± 48.6 OG0021050± 520 OG0032220± 542

Title	Measurements
	OG00070.3± 13.5 OG001231± 65.4 OG002890± 718 OG0031270± 772

Title	Measurements
	OG00091.2± 15.4 OG001247± 59.1 OG002788± 566 OG0031200± 414

Title	Measurements
	OG000205± 43.5 OG001426± 94.0 OG0021380± 802 OG0032680± 789

Title	Measurements
	OG00074.2± 14.2 OG001246± 68.2 OG0021010± 880 OG0031590± 882

Title	Measurements
	OG000105± 28.7 OG001295± 87.6 OG0021050± 752 OG0031480± 586

Title	Measurements
	OG00059.5± 10.1 OG00170.0± 9.62 OG002102± 83.2 OG00383.0± 21.0

Title	Measurements
	OG0001150± 456 OG0011150± 573 OG0021510± 571 OG0031280± 399

Title	Measurements
	OG00010.8± 1.42 OG00111.3± 3.38 OG00214.5± 6.71 OG00311.4± 2.81

Title	Measurements
	OG0009.09± 3.26 OG0019.07± 2.40 OG0029.66± 2.34 OG0039.21± 3.14

Title	Measurements
	OG00011.2± 2.25 OG00112.2± 4.36 OG00215.5± 5.96 OG00312.9± 3.30

Title	Measurements
	OG0001.33± 0.170 OG0011.07± 0.252 OG0020.971± 0.256 OG0031.13± 0.357

Title	Measurements
	OG0000.514± 0.0489 OG0010.658± 0.0759 OG0020.675± 0.187 OG0030.511± 0.0879

Title	Measurements
	OG0000.495± 0.0561 OG0010.641± 0.0653 OG0020.677± 0.184 OG0030.519± 0.103

Title	Measurements
	OG0001.15± 0.422 OG0011.47± 1.02 OG0021.41± 0.576 OG0030.850± 0.351