Ankylosing Spondylitis, Inflammatory Bowel Diseases, Nonalcoholic Steatohepatitis, Psoriasis, Rheumatoid Arthritis
Conditions
Brief summary
The purpose of this study is to investigate experimental medication BMS-986251 taken by mouth in healthy patients and patients with average to very serious Psoriasis (a condition characterized by itchy, dry skin with a scaly rash).
Interventions
DRUGBMS-986251
Escalating oral dose
OTHERPlacebo
Escalating oral dose
Sponsors
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
For more information regarding Bristol-Myers Squibb Clinical Trial participation, please visit www.BMSStudyConnect.com Inclusion Criteria (Healthy Patients): * Males and females, ages 18 to 55 years, inclusive, at screening * Healthy subjects, as determined by no clinically significant deviations from normal in medical history, physical examination, 12-lead ECGs, vital signs, and clinical laboratory results * Body mass index (BMI) of 18.0 to 30.0 kg/m2, inclusive, at screening * Body weight between 55 kg and 105 kg, inclusive, at screening * Women must not be breastfeeding
Exclusion criteria
(Healthy Patients): * Previous participation in the current study * Participation in a drug study or exposure to any investigational drug or placebo within 2 months prior to (the first) drug administration in the current study * Employees of PRA or the Sponsor and their relatives * Any significant acute or chronic medical condition that presents a potential risk to the subject and/or that may compromise the objectives of the study, including active, or history of, liver disease, or intestinal disorder including irritable bowel syndrome * Current or recent (within 3 months of study treatment administration) gastrointestinal disease that could affect pharmacokinetics; history of cholecystectomy is not allowed Inclusion Criteria (Psoriasis Patients): * Males and females, ages 18 to 70 years, inclusive, at screening * BMI of 18.0 to 35.0 kg/m2, inclusive, at screening * Body weight between 55 kg and 120 kg, inclusive, at screening * Diagnosed with stable chronic plaque psoriasis, for at least 6 months prior to screening and be candidates for either photo-therapy or systemic treatment * Moderate-to-severe intensity of psoriasis as defined by: 1. Affected body surface area (BSA) of ≥10% 2. Psoriasis Area and Severity Index (PASI) ≥12 3. Physician Global Assessment (PGA; 6-point scale) ≥3
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Inhibition at Time t [I(t)] (Part B) | Part B : Days 16, 20, and 24 | Summary of IL-17 Inhibition in Whole Blood Pharmacodynamic (PD) Parameters |
| Renal Clearance [CL(R)] | 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) | 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) | 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) | 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) | Part B : Days 2-14 | 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 to Time of Last Quantifiable Concentration [AUC(0-t)] | 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 That Experienced the Following: Serious Adverse Events (SAEs), Death or an Adverse Event (AE) Leading to Study Discontinuation | 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 Vital Signs | 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. |
| Number of Participants With Potentially Clinically Significant Changes in Electrocardiogram (ECG) Parameters | 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 | 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 |
| Maximum Observed Plasma Concentration (Cmax) | 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 |
| Time of Maximum Observed Plasma Concentration (Tmax) | 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) | 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 |
| Terminal Elimination Half-life, Calculated as 0.693/Kel [t(1/2)] | 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 | 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] | 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)] | 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)%] | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time of Maximum Observed Inhibition [t(Imax)] | Part A: Days 1, 2, 3, 5, 7, 11 ; Part B : Day 1, 2, 16, 20, 24 | Summary of IL-17 Inhibition in Whole Blood Pharmacodynamic (PD) Parameters |
| Time of Inhibition Above 50% [t(I>50%)] | Part A: Days 1, 2, 3, 5, 7, 11 ; Part B : Day 1, 2, 16, 20, 24 | Summary of IL-17 Inhibition in Whole Blood Pharmacodynamic (PD) Parameters |
| Time of Inhibition Above 90% [t(I>90%)] | Part A: Days 1, 2, 3, 5, 7, 11 ; Part B : Day 1, 2, 16, 20, 24 | Summary of IL-17 Inhibition in Whole Blood Pharmacodynamic (PD) Parameters |
| Pre-dose Inhibition [I(Pre)] (Part B) | Part B : Days 2, 4, 7, and 14 | Summary of IL-17 Inhibition in Whole Blood Pharmacodynamic (PD) Parameters |
| Maximum Observed Inhibition [I(Max)] | Part A: Days 1, 2, 3, 5, 7, 11 ; Part B : Day 1, 2, 16, 20, 24 | Summary of IL-17 Inhibition in Whole Blood Pharmacodynamic (PD) Parameters |
Countries
Netherlands
Participant flow
Pre-assignment details
96 participants were enrolled (screened) of whom 36 were screen failures, 22 were approved but not dosed and 38 were randomized in the study.
Participants by arm
| Arm | Count |
|---|---|
| Part A: Placebo Part A Single Ascending Dose (SAD) in Healthy Participants; single escalating oral doses of BMS-986251 or placebo | 9 |
| Part A: BMS-986251 2 mg Part A Single Ascending Dose (SAD) in Healthy Participants; single escalating oral doses of BMS-986251 or placebo | 6 |
| Part A: BMS-986251 6 mg Part A Single Ascending Dose (SAD) in Healthy Participants; single escalating oral doses of BMS-986251 or placebo | 6 |
| Part A: BMS-986251 15 mg Part A Single Ascending Dose (SAD) in Healthy Participants; single escalating oral doses of BMS-986251 or placebo | 6 |
| Part A: BMS-986251 30 mg Part A Single Ascending Dose (SAD) in Healthy Participants; single escalating oral doses of BMS-986251 or placebo | 6 |
| Part A : BMS-986251 60 mg Part A Single Ascending Dose (SAD) in Healthy Participants; single escalating oral doses of BMS-986251 or placebo | 3 |
| Total | 36 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 |
|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Sponsor discontinued the study early | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 |
Baseline characteristics
| Characteristic | Part A: Placebo | Part A: BMS-986251 2 mg | Part A: BMS-986251 6 mg | Part A: BMS-986251 15 mg | Part A: BMS-986251 30 mg | Part A : BMS-986251 60 mg | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 30.9 Years STANDARD_DEVIATION 10.46 | 34.5 Years STANDARD_DEVIATION 7.96 | 32.3 Years STANDARD_DEVIATION 11.64 | 37.2 Years STANDARD_DEVIATION 12.26 | 33.8 Years STANDARD_DEVIATION 12.52 | 29.0 Years STANDARD_DEVIATION 6.56 | 33.1 Years STANDARD_DEVIATION 10.28 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants | 5 Participants | 6 Participants | 6 Participants | 6 Participants | 3 Participants | 35 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 7 Participants | 4 Participants | 4 Participants | 6 Participants | 6 Participants | 3 Participants | 30 Participants |
| Sex: Female, Male Female | 5 Participants | 5 Participants | 2 Participants | 3 Participants | 3 Participants | 0 Participants | 18 Participants |
| Sex: Female, Male Male | 4 Participants | 1 Participants | 4 Participants | 3 Participants | 3 Participants | 3 Participants | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 9 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 3 | 0 / 1 | 0 / 1 |
| other Total, other adverse events | 5 / 9 | 4 / 6 | 4 / 6 | 5 / 6 | 4 / 6 | 3 / 3 | 0 / 1 | 0 / 1 |
| serious Total, serious adverse events | 0 / 9 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 3 | 0 / 1 | 0 / 1 |
Outcome results
Primary
Amount Excreted Unchanged in Urine (% of Dose) [Fe(Urine)%]
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
Time frame: Part A: Days 1, 2, 3, 4, 5, 6, 7 ; Part B : Day 14
Population: All participants who received at least 1 dose of BMS-986251 and had any available concentration-time data. Additionally, the evaluable PK population was defined as participants who had adequate PK profiles.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: BMS-986251 2 mg | Amount Excreted Unchanged in Urine (% of Dose) [Fe(Urine)%] | 0 Percentage of dose | Standard Deviation 0 |
| Part A: BMS-986251 6 mg | Amount Excreted Unchanged in Urine (% of Dose) [Fe(Urine)%] | 0 Percentage of dose | Standard Deviation 0 |
| Part A: BMS-986251 15 mg | Amount Excreted Unchanged in Urine (% of Dose) [Fe(Urine)%] | 0.012 Percentage of dose | Standard Deviation 0.011 |
| Part A: BMS-986251 30 mg | Amount Excreted Unchanged in Urine (% of Dose) [Fe(Urine)%] | 0.031 Percentage of dose | Standard Deviation 0.007 |
| Part A : BMS-986251 60 mg | Amount Excreted Unchanged in Urine (% of Dose) [Fe(Urine)%] | 0.033 Percentage of dose | Standard Deviation 0.018 |
| Part B: 3 mg QD (Once Daily) | Amount Excreted Unchanged in Urine (% of Dose) [Fe(Urine)%] | NA Percentage of dose | — |
Primary
Apparent (Oral) Clearance (CL/F) Calculated as Dose/[AUC(0-inf)] for Single Dose
PK parameters were derived from BMS-986251 concentration versus time data measured at the time points specified
Time frame: Part A: Day 1, Part B: Day 14
Population: All participants who received at least 1 dose of BMS-986251 and had any available concentration-time data. Additionally, the evaluable PK population was defined as participants who had adequate PK profiles.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: BMS-986251 2 mg | Apparent (Oral) Clearance (CL/F) Calculated as Dose/[AUC(0-inf)] for Single Dose | 0.343 L/h | Standard Deviation 0.076 |
| Part A: BMS-986251 6 mg | Apparent (Oral) Clearance (CL/F) Calculated as Dose/[AUC(0-inf)] for Single Dose | 0.400 L/h | Standard Deviation 0.1 |
| Part A: BMS-986251 15 mg | Apparent (Oral) Clearance (CL/F) Calculated as Dose/[AUC(0-inf)] for Single Dose | 0.419 L/h | Standard Deviation 0.109 |
| Part A: BMS-986251 30 mg | Apparent (Oral) Clearance (CL/F) Calculated as Dose/[AUC(0-inf)] for Single Dose | 0.411 L/h | Standard Deviation 0.078 |
| Part A : BMS-986251 60 mg | Apparent (Oral) Clearance (CL/F) Calculated as Dose/[AUC(0-inf)] for Single Dose | 0.469 L/h | Standard Deviation 0.083 |
| Part B: 3 mg QD (Once Daily) | Apparent (Oral) Clearance (CL/F) Calculated as Dose/[AUC(0-inf)] for Single Dose | NA L/h | — |
Primary
Apparent Volume of Distribution at Terminal Phase [V(z)/F]
PK parameters were derived from BMS-986251 concentration versus time data measured at the time points specified
Time frame: Part A: Days 1, 2, 3, 4, 5, 6, 7, 9, 11; Part B : Day 14
Population: All participants who received at least 1 dose of BMS-986251 and had any available concentration-time data. Additionally, the evaluable PK population was defined as participants who had adequate PK profiles.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: BMS-986251 2 mg | Apparent Volume of Distribution at Terminal Phase [V(z)/F] | 34.1 L | Standard Deviation 6.39 |
| Part A: BMS-986251 6 mg | Apparent Volume of Distribution at Terminal Phase [V(z)/F] | 35.3 L | Standard Deviation 8.52 |
| Part A: BMS-986251 15 mg | Apparent Volume of Distribution at Terminal Phase [V(z)/F] | 30.6 L | Standard Deviation 5.54 |
| Part A: BMS-986251 30 mg | Apparent Volume of Distribution at Terminal Phase [V(z)/F] | 32.3 L | Standard Deviation 9.44 |
| Part A : BMS-986251 60 mg | Apparent Volume of Distribution at Terminal Phase [V(z)/F] | 32.1 L | Standard Deviation 3.98 |
| Part B: 3 mg QD (Once Daily) | Apparent Volume of Distribution at Terminal Phase [V(z)/F] | NA L | — |
Primary
Area Under the Concentration-time Curve Over 24 Hours (One Dosing Interval) [AUC(0-24)] (Part B)
PK parameters were derived from BMS-986251 concentration versus time data measured at the time points specified
Time frame: Part B : Days 1 and Day 14
Population: All participants who received at least 1 dose of BMS-986251 and had any available concentration-time data. Additionally, the evaluable PK population was defined as participants who had adequate PK profiles.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Part A: BMS-986251 2 mg | Area Under the Concentration-time Curve Over 24 Hours (One Dosing Interval) [AUC(0-24)] (Part B) | NA ng.h/mL |
Primary
Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinite Time [AUC(0-inf)] (Part A)
PK parameters were derived from BMS-986251 concentration versus time data measured at the time points specified
Time frame: Part A: Days 1, 2, 3, 4, 5, 6, 7, 9, 11
Population: All participants who received at least 1 dose of BMS-986251 and had any available concentration-time data. Additionally, the evaluable PK population was defined as participants who had adequate PK profiles.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: BMS-986251 2 mg | Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinite Time [AUC(0-inf)] (Part A) | 6052 ng.h/mL | Standard Deviation 1221 |
| Part A: BMS-986251 6 mg | Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinite Time [AUC(0-inf)] (Part A) | 15815 ng.h/mL | Standard Deviation 3926 |
| Part A: BMS-986251 15 mg | Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinite Time [AUC(0-inf)] (Part A) | 38080 ng.h/mL | Standard Deviation 10827 |
| Part A: BMS-986251 30 mg | Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinite Time [AUC(0-inf)] (Part A) | 75335 ng.h/mL | Standard Deviation 14726 |
| Part A : BMS-986251 60 mg | Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinite Time [AUC(0-inf)] (Part A) | 130873 ng.h/mL | Standard Deviation 24294 |
Primary
Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration [AUC(0-t)]
PK parameters were derived from BMS-986251 concentration versus time data measured at the time points specified
Time frame: Part A: Days 1, 2, 3, 4, 5, 6, 7, 9, 11; Part B : Day 1 and 14
Population: All participants who received at least 1 dose of BMS-986251 and had any available concentration-time data. Additionally, the evaluable PK population was defined as participants who had adequate PK profiles.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: BMS-986251 2 mg | Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration [AUC(0-t)] | 5530 ng.h/mL | Standard Deviation 954 |
| Part A: BMS-986251 6 mg | Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration [AUC(0-t)] | 14737 ng.h/mL | Standard Deviation 3339 |
| Part A: BMS-986251 15 mg | Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration [AUC(0-t)] | 36318 ng.h/mL | Standard Deviation 9554 |
| Part A: BMS-986251 30 mg | Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration [AUC(0-t)] | 71172 ng.h/mL | Standard Deviation 13328 |
| Part A : BMS-986251 60 mg | Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration [AUC(0-t)] | 126198 ng.h/mL | Standard Deviation 21811 |
| Part B: 3 mg QD (Once Daily) | Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration [AUC(0-t)] | NA ng.h/mL | — |
Primary
Cumulative Urinary Excretion (of the Unchanged Drug) [Ae(t)]
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
Time frame: Part A: Days 1, 2, 3, 4, 5, 6, 7 ; Part B : Day 14
Population: All participants who received at least 1 dose of BMS-986251 and had any available concentration-time data. Additionally, the evaluable PK population was defined as participants who had adequate PK profiles.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: BMS-986251 2 mg | Cumulative Urinary Excretion (of the Unchanged Drug) [Ae(t)] | 0 mg | Standard Deviation 0 |
| Part A: BMS-986251 6 mg | Cumulative Urinary Excretion (of the Unchanged Drug) [Ae(t)] | 0 mg | Standard Deviation 0 |
| Part A: BMS-986251 15 mg | Cumulative Urinary Excretion (of the Unchanged Drug) [Ae(t)] | 0.002 mg | Standard Deviation 0.002 |
| Part A: BMS-986251 30 mg | Cumulative Urinary Excretion (of the Unchanged Drug) [Ae(t)] | 0.009 mg | Standard Deviation 0.002 |
| Part A : BMS-986251 60 mg | Cumulative Urinary Excretion (of the Unchanged Drug) [Ae(t)] | 0.020 mg | Standard Deviation 0.011 |
| Part B: 3 mg QD (Once Daily) | Cumulative Urinary Excretion (of the Unchanged Drug) [Ae(t)] | NA mg | — |
Primary
Inhibition at Time t [I(t)] (Part B)
Summary of IL-17 Inhibition in Whole Blood Pharmacodynamic (PD) Parameters
Time frame: Part B : Days 16, 20, and 24
Population: All participants who received at least 1 dose of BMS-986251 or placebo and had any available concentration-time data for the PD assessments. Additionally, the evaluable PD population was defined as participants who had adequate PD profiles.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Part A: Placebo | Inhibition at Time t [I(t)] (Part B) | NA Percent inhibition |
| Part A: BMS-986251 2 mg | Inhibition at Time t [I(t)] (Part B) | NA Percent inhibition |
Primary
Maximum Observed Plasma Concentration (Cmax)
PK parameters were derived from BMS-986251 concentration versus time data measured at the time points specified
Time frame: Part A: Days 1, 2, 3, 4, 5, 6, 7, 9, 11; Part B : Day 1 and 14
Population: All participants who received at least 1 dose of BMS-986251 and had any available concentration-time data. Additionally, the evaluable PK population was defined as participants who had adequate PK profiles.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: BMS-986251 2 mg | Maximum Observed Plasma Concentration (Cmax) | 74.3 ng/mL | Standard Deviation 5.88 |
| Part A: BMS-986251 6 mg | Maximum Observed Plasma Concentration (Cmax) | 206 ng/mL | Standard Deviation 55.8 |
| Part A: BMS-986251 15 mg | Maximum Observed Plasma Concentration (Cmax) | 659 ng/mL | Standard Deviation 207 |
| Part A: BMS-986251 30 mg | Maximum Observed Plasma Concentration (Cmax) | 1131 ng/mL | Standard Deviation 278 |
| Part A : BMS-986251 60 mg | Maximum Observed Plasma Concentration (Cmax) | 2147 ng/mL | Standard Deviation 175 |
| Part B: 3 mg QD (Once Daily) | Maximum Observed Plasma Concentration (Cmax) | NA ng/mL | — |
Primary
Number of Participants That Experienced the Following: Serious Adverse Events (SAEs), Death or an Adverse Event (AE) Leading to Study Discontinuation
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
Time frame: 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)
Population: All participants who had received at least one dose of BMS-986251 or placebo.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A: Placebo | Number of Participants That Experienced the Following: Serious Adverse Events (SAEs), Death or an Adverse Event (AE) Leading to Study Discontinuation | % of participants that experienced SAEs | 0 Participants |
| Part A: Placebo | Number of Participants That Experienced the Following: Serious Adverse Events (SAEs), Death or an Adverse Event (AE) Leading to Study Discontinuation | % of participants with AE leading to study discon. | 0 Participants |
| Part A: Placebo | Number of Participants That Experienced the Following: Serious Adverse Events (SAEs), Death or an Adverse Event (AE) Leading to Study Discontinuation | % of participants that died | 0 Participants |
| Part A: BMS-986251 2 mg | Number of Participants That Experienced the Following: Serious Adverse Events (SAEs), Death or an Adverse Event (AE) Leading to Study Discontinuation | % of participants with AE leading to study discon. | 0 Participants |
| Part A: BMS-986251 2 mg | Number of Participants That Experienced the Following: Serious Adverse Events (SAEs), Death or an Adverse Event (AE) Leading to Study Discontinuation | % of participants that died | 0 Participants |
| Part A: BMS-986251 2 mg | Number of Participants That Experienced the Following: Serious Adverse Events (SAEs), Death or an Adverse Event (AE) Leading to Study Discontinuation | % of participants that experienced SAEs | 0 Participants |
| Part A: BMS-986251 6 mg | Number of Participants That Experienced the Following: Serious Adverse Events (SAEs), Death or an Adverse Event (AE) Leading to Study Discontinuation | % of participants with AE leading to study discon. | 0 Participants |
| Part A: BMS-986251 6 mg | Number of Participants That Experienced the Following: Serious Adverse Events (SAEs), Death or an Adverse Event (AE) Leading to Study Discontinuation | % of participants that experienced SAEs | 0 Participants |
| Part A: BMS-986251 6 mg | Number of Participants That Experienced the Following: Serious Adverse Events (SAEs), Death or an Adverse Event (AE) Leading to Study Discontinuation | % of participants that died | 0 Participants |
| Part A: BMS-986251 15 mg | Number of Participants That Experienced the Following: Serious Adverse Events (SAEs), Death or an Adverse Event (AE) Leading to Study Discontinuation | % of participants that experienced SAEs | 0 Participants |
| Part A: BMS-986251 15 mg | Number of Participants That Experienced the Following: Serious Adverse Events (SAEs), Death or an Adverse Event (AE) Leading to Study Discontinuation | % of participants that died | 0 Participants |
| Part A: BMS-986251 15 mg | Number of Participants That Experienced the Following: Serious Adverse Events (SAEs), Death or an Adverse Event (AE) Leading to Study Discontinuation | % of participants with AE leading to study discon. | 0 Participants |
| Part A: BMS-986251 30 mg | Number of Participants That Experienced the Following: Serious Adverse Events (SAEs), Death or an Adverse Event (AE) Leading to Study Discontinuation | % of participants that died | 0 Participants |
| Part A: BMS-986251 30 mg | Number of Participants That Experienced the Following: Serious Adverse Events (SAEs), Death or an Adverse Event (AE) Leading to Study Discontinuation | % of participants that experienced SAEs | 0 Participants |
| Part A: BMS-986251 30 mg | Number of Participants That Experienced the Following: Serious Adverse Events (SAEs), Death or an Adverse Event (AE) Leading to Study Discontinuation | % of participants with AE leading to study discon. | 0 Participants |
| Part A : BMS-986251 60 mg | Number of Participants That Experienced the Following: Serious Adverse Events (SAEs), Death or an Adverse Event (AE) Leading to Study Discontinuation | % of participants that died | 0 Participants |
| Part A : BMS-986251 60 mg | Number of Participants That Experienced the Following: Serious Adverse Events (SAEs), Death or an Adverse Event (AE) Leading to Study Discontinuation | % of participants that experienced SAEs | 0 Participants |
| Part A : BMS-986251 60 mg | Number of Participants That Experienced the Following: Serious Adverse Events (SAEs), Death or an Adverse Event (AE) Leading to Study Discontinuation | % of participants with AE leading to study discon. | 0 Participants |
| Part B: Placebo | Number of Participants That Experienced the Following: Serious Adverse Events (SAEs), Death or an Adverse Event (AE) Leading to Study Discontinuation | % of participants that died | 0 Participants |
| Part B: Placebo | Number of Participants That Experienced the Following: Serious Adverse Events (SAEs), Death or an Adverse Event (AE) Leading to Study Discontinuation | % of participants that experienced SAEs | 0 Participants |
| Part B: Placebo | Number of Participants That Experienced the Following: Serious Adverse Events (SAEs), Death or an Adverse Event (AE) Leading to Study Discontinuation | % of participants with AE leading to study discon. | 0 Participants |
| Part B: 3 mg QD (Once Daily) | Number of Participants That Experienced the Following: Serious Adverse Events (SAEs), Death or an Adverse Event (AE) Leading to Study Discontinuation | % of participants that experienced SAEs | 0 Participants |
| Part B: 3 mg QD (Once Daily) | Number of Participants That Experienced the Following: Serious Adverse Events (SAEs), Death or an Adverse Event (AE) Leading to Study Discontinuation | % of participants that died | 0 Participants |
| Part B: 3 mg QD (Once Daily) | Number of Participants That Experienced the Following: Serious Adverse Events (SAEs), Death or an Adverse Event (AE) Leading to Study Discontinuation | % of participants with AE leading to study discon. | 0 Participants |
Primary
Number of Participants With Potentially Clinically Significant Changes in Clinical Laboratory Parameters
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
Time frame: Part A: Days 2, 4, 7 and 11; Part B: Days 3, 7, 10, 14, 16, 24
Population: All participants who had received at least one dose of BMS-986251 or placebo.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: Placebo | Number of Participants With Potentially Clinically Significant Changes in Clinical Laboratory Parameters | 0 Participants |
| Part A: BMS-986251 2 mg | Number of Participants With Potentially Clinically Significant Changes in Clinical Laboratory Parameters | 0 Participants |
| Part A: BMS-986251 6 mg | Number of Participants With Potentially Clinically Significant Changes in Clinical Laboratory Parameters | 0 Participants |
| Part A: BMS-986251 15 mg | Number of Participants With Potentially Clinically Significant Changes in Clinical Laboratory Parameters | 0 Participants |
| Part A: BMS-986251 30 mg | Number of Participants With Potentially Clinically Significant Changes in Clinical Laboratory Parameters | 0 Participants |
| Part A : BMS-986251 60 mg | Number of Participants With Potentially Clinically Significant Changes in Clinical Laboratory Parameters | 0 Participants |
| Part B: Placebo | Number of Participants With Potentially Clinically Significant Changes in Clinical Laboratory Parameters | 0 Participants |
| Part B: 3 mg QD (Once Daily) | Number of Participants With Potentially Clinically Significant Changes in Clinical Laboratory Parameters | 0 Participants |
Primary
Number of Participants With Potentially Clinically Significant Changes in Electrocardiogram (ECG) Parameters
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
Time frame: Part A: Days 1, 2, 3,5, 7 and 11; Part B: Days 1, 2, 4, 6, 8, 10, and 12,24
Population: All participants who had received at least one dose of BMS-986251 or placebo.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: Placebo | Number of Participants With Potentially Clinically Significant Changes in Electrocardiogram (ECG) Parameters | 0 Participants |
| Part A: BMS-986251 2 mg | Number of Participants With Potentially Clinically Significant Changes in Electrocardiogram (ECG) Parameters | 0 Participants |
| Part A: BMS-986251 6 mg | Number of Participants With Potentially Clinically Significant Changes in Electrocardiogram (ECG) Parameters | 0 Participants |
| Part A: BMS-986251 15 mg | Number of Participants With Potentially Clinically Significant Changes in Electrocardiogram (ECG) Parameters | 0 Participants |
| Part A: BMS-986251 30 mg | Number of Participants With Potentially Clinically Significant Changes in Electrocardiogram (ECG) Parameters | 0 Participants |
| Part A : BMS-986251 60 mg | Number of Participants With Potentially Clinically Significant Changes in Electrocardiogram (ECG) Parameters | 0 Participants |
| Part B: Placebo | Number of Participants With Potentially Clinically Significant Changes in Electrocardiogram (ECG) Parameters | 0 Participants |
| Part B: 3 mg QD (Once Daily) | Number of Participants With Potentially Clinically Significant Changes in Electrocardiogram (ECG) Parameters | 0 Participants |
Primary
Number of Participants With Potentially Clinically Significant Changes in Vital Signs
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.
Time frame: Part A: Days 1, 2, 3, 4, 5, 6, 7, 9 and 11; Part B: Days 1, 2-13, 15, 16, 18, 20, 24
Population: All participants who had received at least one dose of BMS-986251 or placebo.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: Placebo | Number of Participants With Potentially Clinically Significant Changes in Vital Signs | 0 Participants |
| Part A: BMS-986251 2 mg | Number of Participants With Potentially Clinically Significant Changes in Vital Signs | 0 Participants |
| Part A: BMS-986251 6 mg | Number of Participants With Potentially Clinically Significant Changes in Vital Signs | 0 Participants |
| Part A: BMS-986251 15 mg | Number of Participants With Potentially Clinically Significant Changes in Vital Signs | 0 Participants |
| Part A: BMS-986251 30 mg | Number of Participants With Potentially Clinically Significant Changes in Vital Signs | 0 Participants |
| Part A : BMS-986251 60 mg | Number of Participants With Potentially Clinically Significant Changes in Vital Signs | 0 Participants |
| Part B: Placebo | Number of Participants With Potentially Clinically Significant Changes in Vital Signs | 0 Participants |
| Part B: 3 mg QD (Once Daily) | Number of Participants With Potentially Clinically Significant Changes in Vital Signs | 0 Participants |
Primary
Pre-dose Plasma Concentration (Cpre) (Part B)
PK parameters were derived from BMS-986251 concentration versus time data measured at the time points specified
Time frame: Part B : Days 2-14
Population: All participants who received at least 1 dose of BMS-986251 and had any available concentration-time data. Additionally, the evaluable PK population was defined as participants who had adequate PK profiles.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Part A: BMS-986251 2 mg | Pre-dose Plasma Concentration (Cpre) (Part B) | NA ng/mL |
Primary
Ratio of AUC(0-24) Following Last Dose to AUC(0-24) Following First Dose [AR[AUC(0-24)]] (Part B)
PK parameters were derived from BMS-986251 concentration versus time data measured at the time points specified
Time frame: Part B : Day 14
Population: All participants who received at least 1 dose of BMS-986251 and had any available concentration-time data. Additionally, the evaluable PK population was defined as participants who had adequate PK profiles.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Part A: BMS-986251 2 mg | Ratio of AUC(0-24) Following Last Dose to AUC(0-24) Following First Dose [AR[AUC(0-24)]] (Part B) | NA Ratio |
Primary
Ratio of Cmax Following Last Dose to Cmax Following First Dose [AR(Cmax)] (Part B)
PK parameters were derived from BMS-986251 concentration versus time data measured at the time points specified
Time frame: Part B : Day 14
Population: All participants who received at least 1 dose of BMS-986251 and had any available concentration-time data. Additionally, the evaluable PK population was defined as participants who had adequate PK profiles.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Part A: BMS-986251 2 mg | Ratio of Cmax Following Last Dose to Cmax Following First Dose [AR(Cmax)] (Part B) | NA Ratio |
Primary
Renal Clearance [CL(R)]
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
Time frame: Part A: Days 1, 2, 3, 4, 5, 6, 7 ; Part B : Day 14
Population: All participants who received at least 1 dose of BMS-986251 and had any available concentration-time data. Additionally, the evaluable PK population was defined as participants who had adequate PK profiles.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: BMS-986251 2 mg | Renal Clearance [CL(R)] | 0 L/h | Standard Deviation 0 |
| Part A: BMS-986251 6 mg | Renal Clearance [CL(R)] | 0 L/h | Standard Deviation 0 |
| Part A: BMS-986251 15 mg | Renal Clearance [CL(R)] | 0.00005 L/h | Standard Deviation 0.00004 |
| Part A: BMS-986251 30 mg | Renal Clearance [CL(R)] | 0.00016 L/h | Standard Deviation 0.00006 |
| Part A : BMS-986251 60 mg | Renal Clearance [CL(R)] | 0.00019 L/h | Standard Deviation 0.00012 |
| Part B: 3 mg QD (Once Daily) | Renal Clearance [CL(R)] | NA L/h | — |
Primary
Terminal Elimination Half-life, Calculated as 0.693/Kel [t(1/2)]
PK parameters were derived from BMS-986251 concentration versus time data measured at the time points specified
Time frame: Part A: Days 1, 2, 3, 4, 5, 6, 7, 9, 11; Part B : Day 14
Population: All participants who received at least 1 dose of BMS-986251 and had any available concentration-time data. Additionally, the evaluable PK population was defined as participants who had adequate PK profiles.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: BMS-986251 2 mg | Terminal Elimination Half-life, Calculated as 0.693/Kel [t(1/2)] | 70.9 h | Standard Deviation 16.5 |
| Part A: BMS-986251 6 mg | Terminal Elimination Half-life, Calculated as 0.693/Kel [t(1/2)] | 62.6 h | Standard Deviation 15 |
| Part A: BMS-986251 15 mg | Terminal Elimination Half-life, Calculated as 0.693/Kel [t(1/2)] | 52.2 h | Standard Deviation 9.02 |
| Part A: BMS-986251 30 mg | Terminal Elimination Half-life, Calculated as 0.693/Kel [t(1/2)] | 54.6 h | Standard Deviation 13.6 |
| Part A : BMS-986251 60 mg | Terminal Elimination Half-life, Calculated as 0.693/Kel [t(1/2)] | 48.2 h | Standard Deviation 7.02 |
| Part B: 3 mg QD (Once Daily) | Terminal Elimination Half-life, Calculated as 0.693/Kel [t(1/2)] | NA h | — |
Primary
Time of Maximum Observed Plasma Concentration (Tmax)
PK parameters were derived from BMS-986251 concentration versus time data measured at the time points specified
Time frame: Part A: Days 1, 2, 3, 4, 5, 6, 7, 9, 11; Part B : Day 1 and 14
Population: All participants who received at least 1 dose of BMS-986251 and had any available concentration-time data. Additionally, the evaluable PK population was defined as participants who had adequate PK profiles.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A: BMS-986251 2 mg | Time of Maximum Observed Plasma Concentration (Tmax) | 3.50 h |
| Part A: BMS-986251 6 mg | Time of Maximum Observed Plasma Concentration (Tmax) | 2.27 h |
| Part A: BMS-986251 15 mg | Time of Maximum Observed Plasma Concentration (Tmax) | 1.53 h |
| Part A: BMS-986251 30 mg | Time of Maximum Observed Plasma Concentration (Tmax) | 2.53 h |
| Part A : BMS-986251 60 mg | Time of Maximum Observed Plasma Concentration (Tmax) | 1.05 h |
| Part B: 3 mg QD (Once Daily) | Time of Maximum Observed Plasma Concentration (Tmax) | NA h |
Secondary
Maximum Observed Inhibition [I(Max)]
Summary of IL-17 Inhibition in Whole Blood Pharmacodynamic (PD) Parameters
Time frame: Part A: Days 1, 2, 3, 5, 7, 11 ; Part B : Day 1, 2, 16, 20, 24
Population: All participants who received at least 1 dose of BMS-986251 or placebo and had any available concentration-time data for the PD assessments. Additionally, the evaluable PD population was defined as participants who had adequate PD profiles.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Placebo | Maximum Observed Inhibition [I(Max)] | 27.0 Percent inhibition | Standard Deviation 24 |
| Part A: BMS-986251 2 mg | Maximum Observed Inhibition [I(Max)] | 36.9 Percent inhibition | Standard Deviation 9.54 |
| Part A: BMS-986251 6 mg | Maximum Observed Inhibition [I(Max)] | 44.2 Percent inhibition | Standard Deviation 8.89 |
| Part A: BMS-986251 15 mg | Maximum Observed Inhibition [I(Max)] | 58.2 Percent inhibition | Standard Deviation 4.18 |
| Part A: BMS-986251 30 mg | Maximum Observed Inhibition [I(Max)] | 72.7 Percent inhibition | Standard Deviation 11.3 |
| Part A : BMS-986251 60 mg | Maximum Observed Inhibition [I(Max)] | 73.9 Percent inhibition | Standard Deviation 10.9 |
| Part B: Placebo | Maximum Observed Inhibition [I(Max)] | NA Percent inhibition | — |
| Part B: 3 mg QD (Once Daily) | Maximum Observed Inhibition [I(Max)] | NA Percent inhibition | — |
Secondary
Pre-dose Inhibition [I(Pre)] (Part B)
Summary of IL-17 Inhibition in Whole Blood Pharmacodynamic (PD) Parameters
Time frame: Part B : Days 2, 4, 7, and 14
Population: All participants who received at least 1 dose of BMS-986251 or placebo and had any available concentration-time data for the PD assessments. Additionally, the evaluable PD population was defined as participants who had adequate PD profiles.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Part A: Placebo | Pre-dose Inhibition [I(Pre)] (Part B) | NA Percent inhibition |
| Part A: BMS-986251 2 mg | Pre-dose Inhibition [I(Pre)] (Part B) | NA Percent inhibition |
Secondary
Time of Inhibition Above 50% [t(I>50%)]
Summary of IL-17 Inhibition in Whole Blood Pharmacodynamic (PD) Parameters
Time frame: Part A: Days 1, 2, 3, 5, 7, 11 ; Part B : Day 1, 2, 16, 20, 24
Population: All participants who received at least 1 dose of BMS-986251 or placebo and had any available concentration-time data for the PD assessments. Additionally, the evaluable PD population was defined as participants who had adequate PD profiles.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Part A: Placebo | Time of Inhibition Above 50% [t(I>50%)] | NA h |
| Part A: BMS-986251 2 mg | Time of Inhibition Above 50% [t(I>50%)] | NA h |
| Part A: BMS-986251 6 mg | Time of Inhibition Above 50% [t(I>50%)] | NA h |
| Part A: BMS-986251 15 mg | Time of Inhibition Above 50% [t(I>50%)] | NA h |
| Part A: BMS-986251 30 mg | Time of Inhibition Above 50% [t(I>50%)] | NA h |
| Part A : BMS-986251 60 mg | Time of Inhibition Above 50% [t(I>50%)] | NA h |
| Part B: Placebo | Time of Inhibition Above 50% [t(I>50%)] | NA h |
| Part B: 3 mg QD (Once Daily) | Time of Inhibition Above 50% [t(I>50%)] | NA h |
Secondary
Time of Inhibition Above 90% [t(I>90%)]
Summary of IL-17 Inhibition in Whole Blood Pharmacodynamic (PD) Parameters
Time frame: Part A: Days 1, 2, 3, 5, 7, 11 ; Part B : Day 1, 2, 16, 20, 24
Population: All participants who received at least 1 dose of BMS-986251 or placebo and had any available concentration-time data for the PD assessments. Additionally, the evaluable PD population was defined as participants who had adequate PD profiles.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Part A: Placebo | Time of Inhibition Above 90% [t(I>90%)] | NA h |
| Part A: BMS-986251 2 mg | Time of Inhibition Above 90% [t(I>90%)] | NA h |
| Part A: BMS-986251 6 mg | Time of Inhibition Above 90% [t(I>90%)] | NA h |
| Part A: BMS-986251 15 mg | Time of Inhibition Above 90% [t(I>90%)] | NA h |
| Part A: BMS-986251 30 mg | Time of Inhibition Above 90% [t(I>90%)] | NA h |
| Part A : BMS-986251 60 mg | Time of Inhibition Above 90% [t(I>90%)] | NA h |
| Part B: Placebo | Time of Inhibition Above 90% [t(I>90%)] | NA h |
| Part B: 3 mg QD (Once Daily) | Time of Inhibition Above 90% [t(I>90%)] | NA h |
Secondary
Time of Maximum Observed Inhibition [t(Imax)]
Summary of IL-17 Inhibition in Whole Blood Pharmacodynamic (PD) Parameters
Time frame: Part A: Days 1, 2, 3, 5, 7, 11 ; Part B : Day 1, 2, 16, 20, 24
Population: All participants who received at least 1 dose of BMS-986251 or placebo and had any available concentration-time data for the PD assessments. Additionally, the evaluable PD population was defined as participants who had adequate PD profiles.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A: Placebo | Time of Maximum Observed Inhibition [t(Imax)] | 2.00 h |
| Part A: BMS-986251 2 mg | Time of Maximum Observed Inhibition [t(Imax)] | 1.00 h |
| Part A: BMS-986251 6 mg | Time of Maximum Observed Inhibition [t(Imax)] | 13.00 h |
| Part A: BMS-986251 15 mg | Time of Maximum Observed Inhibition [t(Imax)] | 1.00 h |
| Part A: BMS-986251 30 mg | Time of Maximum Observed Inhibition [t(Imax)] | 1.00 h |
| Part A : BMS-986251 60 mg | Time of Maximum Observed Inhibition [t(Imax)] | 2.00 h |
| Part B: Placebo | Time of Maximum Observed Inhibition [t(Imax)] | NA h |
| Part B: 3 mg QD (Once Daily) | Time of Maximum Observed Inhibition [t(Imax)] | NA h |