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

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

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 Overview

• Status: Terminated
• Conditions: Rheumatoid Arthritis; Inflammatory Bowel Diseases; Psoriasis; Nonalcoholic Steatohepatitis; Ankylosing Spondylitis
• Intervention / Treatment: Drug: BMS-986251; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 38
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Groningen, Netherlands, 9728 NZ
    • Local Institution

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A Single Ascending Dose (SAD) in Healthy Patients; Healthy patient will receive single escalating oral doses of BMS-986251 or placebo	Drug: BMS-986251; Escalating oral dose; Other: Placebo; Escalating oral dose
Experimental: Part B Multiple Ascending Dose (MAD) in Healthy Patients; Healthy patients will receive daily escalating oral doses of BMS-986251 or placebo	Drug: BMS-986251; Escalating oral dose; Other: Placebo; Escalating oral dose
Experimental: Part C Multiple Dosing in Psoriasis Patients; Psoriasis patients will receive daily escalating oral doses of BMS-986251 or placebo	Drug: BMS-986251; Escalating oral dose; Other: Placebo; Escalating oral dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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.	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	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	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	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	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	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	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	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	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	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	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	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	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	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	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	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	Part B : Days 2-14
Inhibition at Time t [I(t)] (Part B)	Summary of IL-17 Inhibition in Whole Blood Pharmacodynamic (PD) Parameters	Part B : Days 16, 20, and 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Observed Inhibition [I(Max)]	Summary of IL-17 Inhibition in Whole Blood Pharmacodynamic (PD) Parameters	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	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	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	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	Part B : Days 2, 4, 7, and 14

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb

Publications and helpful links

Helpful Links

• BMS Clinical Trial Patient Recruiting

Study record dates

Study Major Dates

• Study Start (Actual): November 2, 2017
• Primary Completion (Actual): June 26, 2018
• Study Completion (Actual): June 26, 2018

Study Registration Dates

• First Submitted: October 31, 2017
• First Submitted That Met QC Criteria: October 31, 2017
• First Posted (Actual): November 6, 2017

Study Record Updates

• Last Update Posted (Actual): October 21, 2019
• Last Update Submitted That Met QC Criteria: September 26, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Skin Diseases; Infections; Gastrointestinal Diseases; Liver Diseases; Joint Diseases; Musculoskeletal Diseases; Gastroenteritis; Arthritis; Intestinal Diseases; Skin Diseases, Papulosquamous; Spinal Diseases; Bone Diseases; Spondylarthropathies; Spondylarthritis; Bone Diseases, Infectious; Ankylosis; Inflammatory Bowel Diseases; Fatty Liver; Psoriasis; Non-alcoholic Fatty Liver Disease; Spondylitis; Spondylitis, Ankylosing
• Other Study ID Numbers: IM024-005; 2017-003408-38 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No