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

NCT03329885 | Terminated Phase 1 Results

• 2 other identifiers: IM024-0052017-003408-38
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

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).

Conditions

Rheumatoid Arthritis; Psoriasis; Ankylosing Spondylitis; Inflammatory Bowel Diseases; Nonalcoholic Steatohepatitis

Outcome Measures

Primary Outcomes (19)

• 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 Outcomes (5)

• Maximum Observed Inhibition [I(Max)]

  Part A: Days 1, 2, 3, 5, 7, 11 ; Part B : Day 1, 2, 16, 20, 24

• Time of Maximum Observed Inhibition [t(Imax)]

  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%)]

  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%)]

  Part A: Days 1, 2, 3, 5, 7, 11 ; Part B : Day 1, 2, 16, 20, 24

• Pre-dose Inhibition [I(Pre)] (Part B)

  Part B : Days 2, 4, 7, and 14

Study Arms (3)

Part A Single Ascending Dose (SAD) in Healthy Patients

EXPERIMENTAL

Healthy patient will receive single escalating oral doses of BMS-986251 or placebo

Drug: BMS-986251; Other: Placebo

Part B Multiple Ascending Dose (MAD) in Healthy Patients

EXPERIMENTAL

Healthy patients will receive daily escalating oral doses of BMS-986251 or placebo

Drug: BMS-986251; Other: Placebo

Part C Multiple Dosing in Psoriasis Patients

EXPERIMENTAL

Psoriasis patients will receive daily escalating oral doses of BMS-986251 or placebo

Drug: BMS-986251; Other: Placebo

Interventions

BMS-986251 DRUG

Escalating oral dose

Part A Single Ascending Dose (SAD) in Healthy Patients; Part B Multiple Ascending Dose (MAD) in Healthy Patients; Part C Multiple Dosing in Psoriasis Patients

Placebo OTHER

Escalating oral dose

Part A Single Ascending Dose (SAD) in Healthy Patients; Part B Multiple Ascending Dose (MAD) in Healthy Patients; Part C Multiple Dosing in Psoriasis Patients

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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:
• Affected body surface area (BSA) of ≥10%
• Psoriasis Area and Severity Index (PASI) ≥12
• Physician Global Assessment (PGA; 6-point scale) ≥3
• 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

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (1)

Local Institution

Groningen, 9728 NZ, Netherlands

Location

Related Links

• BMS Clinical Trial Patient Recruiting
• Investigator Inquiry Form

MeSH Terms

Conditions

Arthritis, Rheumatoid; Psoriasis; Spondylitis, Ankylosing; Inflammatory Bowel Diseases; Non-alcoholic Fatty Liver Disease

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Skin Diseases, Papulosquamous; Skin Diseases; Axial Spondyloarthritis; Spondylarthropathies; Spondylarthritis; Spondylitis; Spinal Diseases; Bone Diseases; Ankylosis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases; Fatty Liver; Liver Diseases

Limitations and Caveats

Due to the early termination of the study, only one participant was exposed to multiple doses of BMS-986251.

Results Point of Contact

• Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb

clinical.trials@bms.com

Please Email

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 31, 2017
• First Posted: November 6, 2017
• Study Start: November 2, 2017
• Primary Completion: June 26, 2018
• Study Completion: June 26, 2018
• Last Updated: October 21, 2019
• Results First Posted: October 21, 2019

Record last verified: 2019-09

Locations

NL (1)