Clinical trial NCT03329885: 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
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Rheumatoid Arthritis
Psoriasis
Ankylosing Spondylitis
Inflammatory Bowel Diseases
Nonalcoholic Steatohepatitis
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2017-11-06
Enrollment: 38
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


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:

  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

Primary outcomes:
measure: Number of Participants That Experienced the Following: Serious Adverse Events (SAEs), Death or an Adverse Event (AE) Leading to Study Discontinuation
timeFrame: 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)
measure: Number of Participants With Potentially Clinically Significant Changes in Vital Signs
timeFrame: Part A: Days 1, 2, 3, 4, 5, 6, 7, 9 and 11; Part B: Days 1, 2-13, 15, 16, 18, 20, 24
measure: Number of Participants With Potentially Clinically Significant Changes in Electrocardiogram (ECG) Parameters
timeFrame: Part A: Days 1, 2, 3,5, 7 and 11; Part B: Days 1, 2, 4, 6, 8, 10, and 12,24
measure: Number of Participants With Potentially Clinically Significant Changes in Clinical Laboratory Parameters
timeFrame: Part A: Days 2, 4, 7 and 11; Part B: Days 3, 7, 10, 14, 16, 24
measure: Maximum Observed Plasma Concentration (Cmax)
timeFrame: Part A: Days 1, 2, 3, 4, 5, 6, 7, 9, 11; Part B : Day 1 and 14
measure: Time of Maximum Observed Plasma Concentration (Tmax)
timeFrame: Part A: Days 1, 2, 3, 4, 5, 6, 7, 9, 11; Part B : Day 1 and 14
measure: Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration [AUC(0-t)]
timeFrame: Part A: Days 1, 2, 3, 4, 5, 6, 7, 9, 11; Part B : Day 1 and 14
measure: Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinite Time [AUC(0-inf)] (Part A)
timeFrame: Part A: Days 1, 2, 3, 4, 5, 6, 7, 9, 11
measure: Terminal Elimination Half-life, Calculated as 0.693/Kel [t(1/2)]
timeFrame: Part A: Days 1, 2, 3, 4, 5, 6, 7, 9, 11; Part B : Day 14
measure: Apparent (Oral) Clearance (CL/F) Calculated as Dose/[AUC(0-inf)] for Single Dose
timeFrame: Part A: Day 1, Part B: Day 14
measure: Apparent Volume of Distribution at Terminal Phase [V(z)/F]
timeFrame: Part A: Days 1, 2, 3, 4, 5, 6, 7, 9, 11; Part B : Day 14
measure: Cumulative Urinary Excretion (of the Unchanged Drug) [Ae(t)]
timeFrame: Part A: Days 1, 2, 3, 4, 5, 6, 7 ; Part B : Day 14
measure: Amount Excreted Unchanged in Urine (% of Dose) [Fe(Urine)%]
timeFrame: Part A: Days 1, 2, 3, 4, 5, 6, 7 ; Part B : Day 14
measure: Renal Clearance [CL(R)]
timeFrame: Part A: Days 1, 2, 3, 4, 5, 6, 7 ; Part B : Day 14
measure: Area Under the Concentration-time Curve Over 24 Hours (One Dosing Interval) [AUC(0-24)] (Part B)
timeFrame: Part B : Days 1 and Day 14
measure: Ratio of AUC(0-24) Following Last Dose to AUC(0-24) Following First Dose [AR[AUC(0-24)]] (Part B)
timeFrame: Part B : Day 14
measure: Ratio of Cmax Following Last Dose to Cmax Following First Dose [AR(Cmax)] (Part B)
timeFrame: Part B : Day 14
measure: Pre-dose Plasma Concentration (Cpre) (Part B)
timeFrame: Part B : Days 2-14
measure: Inhibition at Time t [I(t)] (Part B)
timeFrame: Part B : Days 16, 20, and 24
Secondary outcomes:
measure: Maximum Observed Inhibition [I(Max)]
timeFrame: Part A: Days 1, 2, 3, 5, 7, 11 ; Part B : Day 1, 2, 16, 20, 24
measure: Time of Maximum Observed Inhibition [t(Imax)]
timeFrame: Part A: Days 1, 2, 3, 5, 7, 11 ; Part B : Day 1, 2, 16, 20, 24
measure: Time of Inhibition Above 50% [t(I>50%)]
timeFrame: Part A: Days 1, 2, 3, 5, 7, 11 ; Part B : Day 1, 2, 16, 20, 24
measure: Time of Inhibition Above 90% [t(I>90%)]
timeFrame: Part A: Days 1, 2, 3, 5, 7, 11 ; Part B : Day 1, 2, 16, 20, 24
measure: Pre-dose Inhibition [I(Pre)] (Part B)
timeFrame: Part B : Days 2, 4, 7, and 14
Other outcomes:
Locations:
city: Groningen
country: Netherlands
facility: Local Institution
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: