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

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 - BMS-986251 SAD (including BA and FE), MAD and proof of mechanism study

Status

Active, not recruiting

Phases

Unknown

Study type

Interventional

Source

NL-OMON

Registry ID

NL-OMON44577

Enrollment

Registered

2017-10-17

Start date

2017-10-31

Completion date

Unknown

Last updated

2024-04-15

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

auto immune disorder Psoriasis

Interventions

Part A: If the volunteer participate in Groups A1 to A6, the volunteer will be given BMS-986251 or placebo once as a drink with a small volume (maximally approximately 6 mL). After administration o

Eligibility

Age

18 Years to 99 Years

Inclusion criteria

Inclusion criteria: - Healthy males and females, ages 18 to 55 years, inclusive, at screening - BMI of 18.0 to 30.0 kg/m2, inclusive, at screening - Body weight between 55 and 105 kg, inclusive, at screening

Exclusion criteria

Exclusion criteria: Suffering from hepatitis B, hepatitis C, cancer or HIV/AIDS. In case of participation in another drug study within 90 days before the start of this study or being a blood donor within 60 days from the start of the study. In case of donating more than 1.5 liters of blood in the 10 months prior the start of this study.

Design outcomes

Primary

Measure	Time frame
Safety and tolerability - Number and percent of subjects that experience the following: SAE, death or an AE leading to study discontinuation, during the study participation or up to 1 month post discontinuation of dosing or last participation in the study for SAE. - Number and percent of subjects with potentially clinically significant changes in ECG parameters, vital signs, or clinical laboratory parameters from Day 1 through the final follow visit. Pharmacokinetics PK parameters will be derived from BMS-986251 concentration versus time data measured at the time points specified in the schedule of assessments for each part of the study. The PK parameters to be assessed are listed in Section 8.5.3. The PK parameters to be evaluated in each part include but are not limited to the following: - Part A: Cmax, tmax, AUC0-t, AUC0-inf, t1/2, CL/F, Vz/F, Aet, Feurine%, CLR - Part B: Day 1: Cmax, tmax, AUC0-t, AUC0-24 Days 2-14: Cpre Day 14: Cmax, tmax, AUC0-t, AUC0-24, CL/F, Vz/F, t1/2, ARAUC0-24, ARCmax, Aet, Feurine%, CLR	—

Measure

Time frame

Safety and tolerability - Number and percent of subjects that experience the following: SAE, death or an AE leading to study discontinuation, during the study participation or up to 1 month post discontinuation of dosing or last participation in the study for SAE. - Number and percent of subjects with potentially clinically significant changes in ECG parameters, vital signs, or clinical laboratory parameters from Day 1 through the final follow visit. Pharmacokinetics PK parameters will be derived from BMS-986251 concentration versus time data measured at the time points specified in the schedule of assessments for each part of the study. The PK parameters to be assessed are listed in Section 8.5.3. The PK parameters to be evaluated in each part include but are not limited to the following: - Part A: Cmax, tmax, AUC0-t, AUC0-inf, t1/2, CL/F, Vz/F, Aet, Feurine%, CLR - Part B: Day 1: Cmax, tmax, AUC0-t, AUC0-24 Days 2-14: Cpre Day 14: Cmax, tmax, AUC0-t, AUC0-24, CL/F, Vz/F, t1/2, ARAUC0-24, ARCmax, Aet, Feurine%, CLR

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Secondary

Measure	Time frame
The secondary objective to assess PD of single and multiple oral doses of BMS 986251 in healthy subjects will be measured by evaluating the percentage ex-vivo inhibition (I) of IL-17 secretion in whole blood. PD parameters will be derived from inhibition versus time data measured at the time points specified in the schedule of assessments for each part of the study. The PD parameters to be assessed are listed in Section 8.5.4. The PD parameters to be evaluated in each part include: - Part A: Imax, tImax, tI>50%, tI>90% - Part B: Imax, tImax, tI>50%, tI>90% (Day 1 and Day 14); Ipre (Days 2, 4, 7, and 14); It (Days 16, 20, and 24) The secondary objectives to evaluate the oral BA of an oral suspension of BMS 986251 relative to a liquid dosage form at a single dose level in healthy subjects, and to evaluate the effect of a high-fat meal on the PK of an oral suspension of BMS-986251 at a single dose level in healthy subjects will be evaluated by comparing the PK parameters listed for the SAD part in Section 9.3.1. The secondary objective to evaluate the efficacy of multiple doses of BMS 986251 in patients with moderate-to-severe psoriasis will be evaluated by evaluating the following endpoints: • PASI score at baseline, and Days 7, 14, and 28 • PGA score at baseline, and Days 7, 14, and 28 • DLQI at baseline, and Days 7, 14, and 28	—

Measure

Time frame

The secondary objective to assess PD of single and multiple oral doses of BMS 986251 in healthy subjects will be measured by evaluating the percentage ex-vivo inhibition (I) of IL-17 secretion in whole blood. PD parameters will be derived from inhibition versus time data measured at the time points specified in the schedule of assessments for each part of the study. The PD parameters to be assessed are listed in Section 8.5.4. The PD parameters to be evaluated in each part include: - Part A: Imax, tImax, tI>50%, tI>90% - Part B: Imax, tImax, tI>50%, tI>90% (Day 1 and Day 14); Ipre (Days 2, 4, 7, and 14); It (Days 16, 20, and 24) The secondary objectives to evaluate the oral BA of an oral suspension of BMS 986251 relative to a liquid dosage form at a single dose level in healthy subjects, and to evaluate the effect of a high-fat meal on the PK of an oral suspension of BMS-986251 at a single dose level in healthy subjects will be evaluated by comparing the PK parameters listed for the SAD part in Section 9.3.1. The secondary objective to evaluate the efficacy of multiple doses of BMS 986251 in patients with moderate-to-severe psoriasis will be evaluated by evaluating the following endpoints: • PASI score at baseline, and Days 7, 14, and 28 • PGA score at baseline, and Days 7, 14, and 28 • DLQI at baseline, and Days 7, 14, and 28

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Countries

Netherlands

Outcome results

None listed

Source: NL-OMON (via WHO ICTRP)