Back to resultsA Study of Experimental Medication BMS-986251, Taken by Mouth, in Healthy Participants and Patients With Average to Very Serious Psoriasis
Primary Purpose
Rheumatoid Arthritis, Psoriasis, Ankylosing Spondylitis
Status
Terminated
Phase
Phase 1
Locations
Netherlands
Study Type
Interventional
Intervention
BMS-986251
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Rheumatoid Arthritis
Eligibility 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:
- Affected body surface area (BSA) of ≥10%
- Psoriasis Area and Severity Index (PASI) ≥12
- 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
Sites / Locations
- Local Institution
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
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
Arm Description
Healthy patient will receive single escalating oral doses of BMS-986251 or placebo
Healthy patients will receive daily escalating oral doses of BMS-986251 or placebo
Psoriasis patients will receive daily escalating oral doses of BMS-986251 or placebo
Outcomes
Primary Outcome Measures
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
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.
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
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
Maximum Observed Plasma Concentration (Cmax)
PK parameters were derived from BMS-986251 concentration versus time data measured at the time points specified
Time of Maximum Observed Plasma Concentration (Tmax)
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)]
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)
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)]
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
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]
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)]
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)%]
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)]
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)
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)
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)
PK parameters were derived from BMS-986251 concentration versus time data measured at the time points specified
Pre-dose Plasma Concentration (Cpre) (Part B)
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)
Summary of IL-17 Inhibition in Whole Blood Pharmacodynamic (PD) Parameters
Secondary Outcome Measures
Maximum Observed Inhibition [I(Max)]
Summary of IL-17 Inhibition in Whole Blood Pharmacodynamic (PD) Parameters
Time of Maximum Observed Inhibition [t(Imax)]
Summary of IL-17 Inhibition in Whole Blood Pharmacodynamic (PD) Parameters
Time of Inhibition Above 50% [t(I>50%)]
Summary of IL-17 Inhibition in Whole Blood Pharmacodynamic (PD) Parameters
Time of Inhibition Above 90% [t(I>90%)]
Summary of IL-17 Inhibition in Whole Blood Pharmacodynamic (PD) Parameters
Pre-dose Inhibition [I(Pre)] (Part B)
Summary of IL-17 Inhibition in Whole Blood Pharmacodynamic (PD) Parameters
Full Information
NCT ID
NCT03329885
First Posted
October 31, 2017
Last Updated
September 26, 2019
Sponsor
Bristol-Myers Squibb
1. Study Identification
Unique Protocol Identification Number
NCT03329885
Brief Title
A Study of Experimental Medication BMS-986251, Taken by Mouth, in Healthy Participants and Patients With Average to Very Serious Psoriasis
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
September 2019
Overall Recruitment Status
Terminated
Why Stopped
Adverse change in the risk/benefit
Study Start Date
November 2, 2017 (Actual)
Primary Completion Date
June 26, 2018 (Actual)
Study Completion Date
June 26, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bristol-Myers Squibb
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rheumatoid Arthritis, Psoriasis, Ankylosing Spondylitis, Inflammatory Bowel Diseases, Nonalcoholic Steatohepatitis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
38 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Part A Single Ascending Dose (SAD) in Healthy Patients
Arm Type
Experimental
Arm Description
Healthy patient will receive single escalating oral doses of BMS-986251 or placebo
Arm Title
Part B Multiple Ascending Dose (MAD) in Healthy Patients
Arm Type
Experimental
Arm Description
Healthy patients will receive daily escalating oral doses of BMS-986251 or placebo
Arm Title
Part C Multiple Dosing in Psoriasis Patients
Arm Type
Experimental
Arm Description
Psoriasis patients will receive daily escalating oral doses of BMS-986251 or placebo
Intervention Type
Drug
Intervention Name(s)
BMS-986251
Intervention Description
Escalating oral dose
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Escalating oral dose
Primary Outcome Measure Information:
Title
Number of Participants That Experienced the Following: Serious Adverse Events (SAEs), Death or an Adverse Event (AE) Leading to Study Discontinuation
Description
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)
Title
Number of Participants With Potentially Clinically Significant Changes in Vital Signs
Description
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
Title
Number of Participants With Potentially Clinically Significant Changes in Electrocardiogram (ECG) Parameters
Description
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
Title
Number of Participants With Potentially Clinically Significant Changes in Clinical Laboratory Parameters
Description
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
Title
Maximum Observed Plasma Concentration (Cmax)
Description
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
Title
Time of Maximum Observed Plasma Concentration (Tmax)
Description
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
Title
Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration [AUC(0-t)]
Description
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
Title
Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinite Time [AUC(0-inf)] (Part A)
Description
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
Title
Terminal Elimination Half-life, Calculated as 0.693/Kel [t(1/2)]
Description
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
Title
Apparent (Oral) Clearance (CL/F) Calculated as Dose/[AUC(0-inf)] for Single Dose
Description
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
Title
Apparent Volume of Distribution at Terminal Phase [V(z)/F]
Description
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
Title
Cumulative Urinary Excretion (of the Unchanged Drug) [Ae(t)]
Description
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
Title
Amount Excreted Unchanged in Urine (% of Dose) [Fe(Urine)%]
Description
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
Title
Renal Clearance [CL(R)]
Description
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
Title
Area Under the Concentration-time Curve Over 24 Hours (One Dosing Interval) [AUC(0-24)] (Part B)
Description
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
Title
Ratio of AUC(0-24) Following Last Dose to AUC(0-24) Following First Dose [AR[AUC(0-24)]] (Part B)
Description
PK parameters were derived from BMS-986251 concentration versus time data measured at the time points specified
Time Frame
Part B : Day 14
Title
Ratio of Cmax Following Last Dose to Cmax Following First Dose [AR(Cmax)] (Part B)
Description
PK parameters were derived from BMS-986251 concentration versus time data measured at the time points specified
Time Frame
Part B : Day 14
Title
Pre-dose Plasma Concentration (Cpre) (Part B)
Description
PK parameters were derived from BMS-986251 concentration versus time data measured at the time points specified
Time Frame
Part B : Days 2-14
Title
Inhibition at Time t [I(t)] (Part B)
Description
Summary of IL-17 Inhibition in Whole Blood Pharmacodynamic (PD) Parameters
Time Frame
Part B : Days 16, 20, and 24
Secondary Outcome Measure Information:
Title
Maximum Observed Inhibition [I(Max)]
Description
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
Title
Time of Maximum Observed Inhibition [t(Imax)]
Description
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
Title
Time of Inhibition Above 50% [t(I>50%)]
Description
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
Title
Time of Inhibition Above 90% [t(I>90%)]
Description
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
Title
Pre-dose Inhibition [I(Pre)] (Part B)
Description
Summary of IL-17 Inhibition in Whole Blood Pharmacodynamic (PD) Parameters
Time Frame
Part B : Days 2, 4, 7, and 14
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility 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:
Affected body surface area (BSA) of ≥10%
Psoriasis Area and Severity Index (PASI) ≥12
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bristol-Myers Squibb
Organizational Affiliation
Bristol-Myers Squibb
Official's Role
Study Director
Facility Information:
Facility Name
Local Institution
City
Groningen
ZIP/Postal Code
9728 NZ
Country
Netherlands
12. IPD Sharing Statement
Links:
URL
http://bms.com/studyconnect/Pages/home.aspx
Description
BMS Clinical Trial Patient Recruiting
Learn more about this trial
A Study of Experimental Medication BMS-986251, Taken by Mouth, in Healthy Participants and Patients With Average to Very Serious Psoriasis
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