A Double-Blind Randomized Placebo-Controlled Single and Multiple Ascending Doses Study of the Safety and Tolerability, Pharmacokinetics (Including Bioavailability Comparison and Food Effect) and Pharmacodynamics of Oral BMS-986251 Administration in Healthy Subjects, With Efficacy Assessment of Multiple Doses in Patients With Moderate-to-Severe Psoriasis

Number of Participants That Experienced the Following: Serious Adverse Events (SAEs), Death or an Adverse Event (AE) Leading to Study Discontinuation

时间窗: AEs: Day 1 to Day 11 (Part A), Day 1 to Day 24 (Part B); SAEs: Day -21 to within 30 days of discontinuation of dosing (Part A), Day -21 to within 30 days of discontinuation of dosing (Part B)

An adverse event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study drug and that does not necessarily have a causal relationship with the treatment. A Serious Adverse Event is defined as any untoward medical occurrence that, at any dose results in death or is life-threatening or requires inpatient hospitalization

Number of Participants With Potentially Clinically Significant Changes in Electrocardiogram (ECG) Parameters

时间窗: Part A: Days 1, 2, 3,5, 7 and 11; Part B: Days 1, 2, 4, 6, 8, 10, and 12,24

The following ECG parameters were recorded: heart rate, PR-interval, QRS-duration, QT-interval, QTcinterval, (Fridericia's) and the interpretation of the ECG profile by the Investigator

Number of Participants With Potentially Clinically Significant Changes in Clinical Laboratory Parameters

时间窗: Part A: Days 2, 4, 7 and 11; Part B: Days 3, 7, 10, 14, 16, 24

Hematology: Hemoglobin, Hematocrit, Total leukocyte count, including differential Platelet count, Red blood cell count, Reticulocyte count; Chemistry: Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Total bilirubin, Direct bilirubin, Alkaline phosphatase, Lactate dehydrogenase , (LDH), Creatinine, Urea, Uric acid, Fasting glucose, High sensitivity C-reactive protein (hs-CRP), Total protein, Albumin Sodium, Potassium, Chloride, Calcium Inorganic phosphate, Magnesium, Creatine kinase, Creatinine clearance (CLcr)- screening only, Cholesterol Triglycerides, High-density lipoprotein (HDL), Low-density lipoprotein (LDL), Urinalysis: Protein, Glucose, Blood Leukocyte esterase, Specific gravity, pH,Microscopic examination of the sediment if blood, protein or leukocytes esterase are positive on the dipstick; Other Analyses: Urine test for alcohol, Urine test for drugs of abuse, Pregnancy test

Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration [AUC(0-t)]

时间窗: Part A: Days 1, 2, 3, 4, 5, 6, 7, 9, 11; Part B : Day 1 and 14

PK parameters were derived from BMS-986251 concentration versus time data measured at the time points specified

Number of Participants With Potentially Clinically Significant Changes in Vital Signs

时间窗: Part A: Days 1, 2, 3, 4, 5, 6, 7, 9 and 11; Part B: Days 1, 2-13, 15, 16, 18, 20, 24

Vital signs (Systolic and diastolic blood pressure and pulse) were recorded after the participant had been resting for at least 5 minutes in the supine position.

Maximum Observed Plasma Concentration (Cmax)

时间窗: Part A: Days 1, 2, 3, 4, 5, 6, 7, 9, 11; Part B : Day 1 and 14

PK parameters were derived from BMS-986251 concentration versus time data measured at the time points specified

Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinite Time [AUC(0-inf)] (Part A)

时间窗: Part A: Days 1, 2, 3, 4, 5, 6, 7, 9, 11

PK parameters were derived from BMS-986251 concentration versus time data measured at the time points specified

Time of Maximum Observed Plasma Concentration (Tmax)

时间窗: Part A: Days 1, 2, 3, 4, 5, 6, 7, 9, 11; Part B : Day 1 and 14

PK parameters were derived from BMS-986251 concentration versus time data measured at the time points specified

Terminal Elimination Half-life, Calculated as 0.693/Kel [t(1/2)]

时间窗: Part A: Days 1, 2, 3, 4, 5, 6, 7, 9, 11; Part B : Day 14

PK parameters were derived from BMS-986251 concentration versus time data measured at the time points specified

Apparent (Oral) Clearance (CL/F) Calculated as Dose/[AUC(0-inf)] for Single Dose

时间窗: Part A: Day 1, Part B: Day 14

PK parameters were derived from BMS-986251 concentration versus time data measured at the time points specified

Apparent Volume of Distribution at Terminal Phase [V(z)/F]

时间窗: Part A: Days 1, 2, 3, 4, 5, 6, 7, 9, 11; Part B : Day 14

PK parameters were derived from BMS-986251 concentration versus time data measured at the time points specified

Cumulative Urinary Excretion (of the Unchanged Drug) [Ae(t)]

时间窗: Part A: Days 1, 2, 3, 4, 5, 6, 7 ; Part B : Day 14

Summary of BMS-986251 Excretion Parameters in Urine. PK parameters were derived from BMS-986251 concentration versus time data measured at the time points specified

Amount Excreted Unchanged in Urine (% of Dose) [Fe(Urine)%]

时间窗: Part A: Days 1, 2, 3, 4, 5, 6, 7 ; Part B : Day 14

Summary of BMS-986251 Excretion Parameters in Urine. PK parameters were derived from BMS-986251 concentration versus time data measured at the time points specified

Renal Clearance [CL(R)]

时间窗: Part A: Days 1, 2, 3, 4, 5, 6, 7 ; Part B : Day 14

Summary of BMS-986251 Excretion Parameters in Urine. PK parameters were derived from BMS-986251 concentration versus time data measured at the time points specified

Area Under the Concentration-time Curve Over 24 Hours (One Dosing Interval) [AUC(0-24)] (Part B)

时间窗: Part B : Days 1 and Day 14

PK parameters were derived from BMS-986251 concentration versus time data measured at the time points specified

Ratio of AUC(0-24) Following Last Dose to AUC(0-24) Following First Dose [AR[AUC(0-24)]] (Part B)

时间窗: Part B : Day 14

PK parameters were derived from BMS-986251 concentration versus time data measured at the time points specified

Ratio of Cmax Following Last Dose to Cmax Following First Dose [AR(Cmax)] (Part B)

时间窗: Part B : Day 14

PK parameters were derived from BMS-986251 concentration versus time data measured at the time points specified

Pre-dose Plasma Concentration (Cpre) (Part B)

时间窗: Part B : Days 2-14

PK parameters were derived from BMS-986251 concentration versus time data measured at the time points specified

Inhibition at Time t [I(t)] (Part B)

时间窗: Part B : Days 16, 20, and 24

Summary of IL-17 Inhibition in Whole Blood Pharmacodynamic (PD) Parameters