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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT03329885
• Date of registration: 31/10/2017
• Prospective Registration: Yes
• Primary sponsor: Bristol-Myers Squibb
• Public title: A Study of Experimental Medication BMS-986251, Taken by Mouth, in Healthy Participants and Patients With Average to Very Serious Psoriasis
• Scientific 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
• Date of first enrolment: November 2, 2017
• Target sample size: 38
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/show/NCT03329885
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 1/Phase 2

Countries of recruitment

Netherlands

Contacts

• Name: Bristol-Myers Squibb
• Affiliation: Bristol-Myers Squibb

Key inclusion & exclusion 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



Age minimum: 18 Years
Age maximum: 70 Years
Gender: All

Health Condition(s) or Problem(s) studied

Nonalcoholic Steatohepatitis

Psoriasis

Inflammatory Bowel Diseases

Ankylosing Spondylitis

Rheumatoid Arthritis

Intervention(s)

Drug: BMS-986251

Other: Placebo

Primary Outcome(s)

Cumulative Urinary Excretion (of the Unchanged Drug) [Ae(t)] [Time Frame: Part A: Days 1, 2, 3, 4, 5, 6, 7 ; Part B : Day 14]

Number of Participants With Potentially Clinically Significant Changes in Vital Signs [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]

Ratio of Cmax Following Last Dose to Cmax Following First Dose [AR(Cmax)] (Part B) [Time Frame: Part B : Day 14]

Inhibition at Time t [I(t)] (Part B) [Time Frame: Part B : Days 16, 20, and 24]

Time of Maximum Observed Plasma Concentration (Tmax) [Time Frame: Part A: Days 1, 2, 3, 4, 5, 6, 7, 9, 11; Part B : Day 1 and 14]

Apparent Volume of Distribution at Terminal Phase [V(z)/F] [Time Frame: Part A: Days 1, 2, 3, 4, 5, 6, 7, 9, 11; Part B : Day 14]

Amount Excreted Unchanged in Urine (% of Dose) [Fe(Urine)%] [Time Frame: Part A: Days 1, 2, 3, 4, 5, 6, 7 ; Part B : Day 14]

Maximum Observed Plasma Concentration (Cmax) [Time Frame: Part A: Days 1, 2, 3, 4, 5, 6, 7, 9, 11; Part B : Day 1 and 14]

Apparent (Oral) Clearance (CL/F) Calculated as Dose/[AUC(0-inf)] for Single Dose [Time Frame: Part A: Day 1, Part B: Day 14]

Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinite Time [AUC(0-inf)] (Part A) [Time Frame: Part A: Days 1, 2, 3, 4, 5, 6, 7, 9, 11]

Number of Participants That Experienced the Following: Serious Adverse Events (SAEs), Death or an Adverse Event (AE) Leading to Study Discontinuation [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)]

Number of Participants With Potentially Clinically Significant Changes in Clinical Laboratory Parameters [Time Frame: Part A: Days 2, 4, 7 and 11; Part B: Days 3, 7, 10, 14, 16, 24]

Area Under the Concentration-time Curve Over 24 Hours (One Dosing Interval) [AUC(0-24)] (Part B) [Time Frame: 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) [Time Frame: Part B : Day 14]

Renal Clearance [CL(R)] [Time Frame: Part A: Days 1, 2, 3, 4, 5, 6, 7 ; Part B : Day 14]

Terminal Elimination Half-life, Calculated as 0.693/Kel [t(1/2)] [Time Frame: Part A: Days 1, 2, 3, 4, 5, 6, 7, 9, 11; Part B : Day 14]

Number of Participants With Potentially Clinically Significant Changes in Electrocardiogram (ECG) Parameters [Time Frame: Part A: Days 1, 2, 3,5, 7 and 11; Part B: Days 1, 2, 4, 6, 8, 10, and 12,24]

Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration [AUC(0-t)] [Time Frame: Part A: Days 1, 2, 3, 4, 5, 6, 7, 9, 11; Part B : Day 1 and 14]

Pre-dose Plasma Concentration (Cpre) (Part B) [Time Frame: Part B : Days 2-14]

Secondary Outcome(s)

Maximum Observed Inhibition [I(Max)] [Time Frame: 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%)] [Time Frame: Part A: Days 1, 2, 3, 5, 7, 11 ; Part B : Day 1, 2, 16, 20, 24]

Pre-dose Inhibition [I(Pre)] (Part B) [Time Frame: Part B : Days 2, 4, 7, and 14]

Time of Maximum Observed Inhibition [t(Imax)] [Time Frame: 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%)] [Time Frame: Part A: Days 1, 2, 3, 5, 7, 11 ; Part B : Day 1, 2, 16, 20, 24]

Secondary ID(s)

IM024-005

2017-003408-38

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 21/10/2019
• URL: https://clinicaltrials.gov/ct2/show/results/NCT03329885