A Study of Experimental Medication BMS-986251, Taken by Mouth, in Healthy Participants and Patients With Average to Very Serious Psoriasis

Phase 2TerminatedNCT03329885

Bristol-Myers Squibb38 enrolled

Overview

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).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Rheumatoid Arthritis Psoriasis Ankylosing Spondylitis Inflammatory Bowel Diseases Nonalcoholic Steatohepatitis

Interventions

BMS-986251DRUG

Escalating oral dose

PlaceboOTHER

Escalating oral dose

Eligibility

Sex: ALLMin age: 18 YearsMax age: 70 YearsHealthy volunteers:

Medical Language ↔ Plain English

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 Exclusion Criteria (Psoriasis 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 Other protocol defined inclusion/exclusion criteria could apply

Locations (1)

Local Institution

Groningen, Netherlands

Outcomes

Primary Outcomes

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)

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

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

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

Data from ClinicalTrials.gov

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Secondary Outcomes

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

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

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

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

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