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

Phase 1

Terminated

• Conditions: Rheumatoid Arthritis; Psoriasis; Ankylosing Spondylitis; Inflammatory Bowel Diseases; Nonalcoholic Steatohepatitis
• Interventions: Drug: BMS-986251; Other: Placebo

• Registration Number: NCT03329885
• Lead Sponsor: Bristol-Myers Squibb

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).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2017-10-31
• Study First Submitted QC: 2017-10-31
• Study Start: 2017-11-02
• Study First Posted: 2017-11-06
• Primary Completion: 2018-06-26
• Study Completion: 2018-06-26
• Results First Submitted: 2019-06-26
• Status Verified: 2019-09
• Results First Submitted QC: 2019-09-26
• Last Update Submitted: 2019-09-26
• Results First Posted: 2019-10-21
• Last Update Posted: 2019-10-21

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 38

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Part A Single Ascending Dose (SAD) in Healthy Patients	Placebo	Healthy patient will receive single escalating oral doses of BMS-986251 or placebo
Part B Multiple Ascending Dose (MAD) in Healthy Patients	Placebo	Healthy patients will receive daily escalating oral doses of BMS-986251 or placebo
Part B Multiple Ascending Dose (MAD) in Healthy Patients	BMS-986251	Healthy patients will receive daily escalating oral doses of BMS-986251 or placebo
Part A Single Ascending Dose (SAD) in Healthy Patients	BMS-986251	Healthy patient will receive single escalating oral doses of BMS-986251 or placebo
Part C Multiple Dosing in Psoriasis Patients	BMS-986251	Psoriasis patients will receive daily escalating oral doses of BMS-986251 or placebo
Part C Multiple Dosing in Psoriasis Patients	Placebo	Psoriasis patients will receive daily escalating oral doses of BMS-986251 or placebo

Primary Outcome Measures

Name	Time	Method
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 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
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 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.
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
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
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
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
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
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

Secondary Outcome Measures

Name	Time	Method
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
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

Trial Locations

Locations (1)

Local Institution; 🇳🇱 Groningen, Netherlands