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| ID | Type | Description | Link |
|---|---|---|---|
| 2013-002323-42 | EudraCT Number |
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| Name | Class |
|---|---|
| Parexel | INDUSTRY |
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To evaluate the safety and tolerability of UCB5857. Part 1 of the study explores single doses of the drug. Part 2 of the study explores giving the drug every day for 14 days. The study uses healthy and psoriasis subjects.
This is a first-in-human (FIH), Phase 1, randomized, double-blind, placebo controlled, single center study designed to evaluate the safety/ tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of UCB5857 following oral administration of single ascending doses (SAD) in healthy subjects (Part 1) and multiple ascending doses (MAD) in healthy and mild-to-moderate psoriatic subjects (Part 2).
The primary objective of this study is to investigate the safety and tolerability of UCB5857 when given as single oral doses in healthy subjects and as ascending multiple oral doses in healthy subjects and mild-to-moderate psoriatic subjects.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| UCB5857 Part 1 | Experimental | Part 1: Subjects assigned to UCB5857 or placebo single dose. |
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| UCB5857 Part 2 | Experimental | Part 2: Subjects assigned to UCB5857 or placebo multiple doses. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| UCB5857 Part 1 | Drug | Active substance: UCB5857 Pharmaceutical form: Capsule Concentration: 1 mg, 5 mg, 10 mg or 15 mg Route of administration: Oral |
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| Measure | Description | Time Frame |
|---|---|---|
| Incidence of adverse events during the study | Day -1 to single dose Day 4 (Part 1) and Day -1 to multiple dose Day 18 (Part 2) |
| Measure | Description | Time Frame |
|---|---|---|
| Area under the plasma concentration-time curve from time 0 to the last quantifiable concentration (AUC(0-t)) | Pharmacokinetic samples will be taken predose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 24, 48 and 72 hours postdose on Day 1 (Part 1 and Part 2) | |
| Area under the plasma concentration-time curve from time 0 to 24 hours (AUC(0-24)) |
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Inclusion Criteria:
Subject is male or female, aged between 18 and 55 years (inclusive).
Female subjects must have a negative serum pregnancy test at Screening, and be of nonchildbearing potential, defined as:
Male subject confirms that, during the study period and for a period of 3 months or 5 half lives after the last administration of the IMP (whichever is longer), when having sexual intercourse with a woman of childbearing potential, a method of highly effective contraception will be used (eg, condom + spermicide, and an additional contraceptive method used by the partner). Male contraception is not required if the male subject has undergone effective vasectomy >3 months prior to the study; however, his female partner must use a contraceptive method during the study period and for a period of 3 months or 5 half-lives after the last administration of the IMP (whichever is longer)
Subject is of normal weight as determined by a body mass index (BMI) of between 18.0 and 30.0 kg/ m2 (inclusive), with a body weight of at least 50 kg (for healthy subjects only)
Subject is in good physical and mental health, in the opinion of the Investigator, determined on the basis of medical history and general clinical examination at Screening
Subject has clinical laboratory test results within the reference ranges of the testing laboratory. Subjects with isolated test results that are outside the specified ranges and that are deemed as clinically nonsignificant will be allowed at the discretion of the Investigator, following discussion with the Sponsor's Study Physician, excluding ALT, AST, alkaline phosphate and bilirubin, which have to be within normal range. If a subject has 1 isolated test result outside the specific range that is deemed clinically significant, rescreening may be allowed at the discretion of the Investigator, following discussion with the Sponsor's Study Physician
Subject has BP and pulse rate within normal range in a supine position after 5 minutes rest (systolic BP: 90 to 140 mmHg, diastolic BP: 50 to 90 mmHg, pulse rate: 40 to 90 bpm). Results that are outside the specified ranges and that are deemed as clinically nonsignificant will be allowed at the discretion of the Investigator, following discussion with the Sponsor's Study Physician. If a subject has 1 isolated finding outside the specific range which is deemed clinically significant, rescreening may be allowed at the discretion of the Investigator, following discussion with the Sponsor's Study Physician
Subject has a body temperature (oral or tympanic) between 35.0 and 37.5°C (95 and 99.5°F) inclusive
Subject's ECG is considered "normal" or "abnormal" but clinically nonsignificant (as interpreted by the Investigator). If the subject has 1 isolated finding outside the specific range that is deemed potentially clinically significant, rescreening may be allowed at the discretion of the Investigator, following discussion with the Sponsor's Study Physician
In addition for the psoriatic subjects cohort
Exclusion Criteria:
Subjects are not permitted to enroll in the study if any of the following criteria is met:
Healthy and psoriatic subjects
Subject is an employee or direct relative of an employee of PAREXEL or the Sponsor
Subject has participated in another study of an investigational medication (or a medical device) within the last 3 months or 5 half-lives of the study medication, whichever is longer, or is currently participating in another study of an investigational medication (or a medical device)
Subject has made a blood donation (>400mL) or had a comparable blood loss (>350 mL) within the 3 months prior to first intake of study drug
Subject tests positive for human immunodeficiency virus-1/2 antibody (HIV-1/2Ab), hepatitis B surface antigen, or hepatitis C virus antibody.
Subject is not willing to avoid heavy physical exertion for 2 days before drug administration and during the study
Subject has a history of alcohol and/or drug abuse up to 6 months before Screening
Subject has an alcohol consumption of more than 21 units (males) or 14 units (females) of alcohol per week (1 unit of alcohol is equivalent to 10 mL ethanol; for example, 330 mL of 5 % alcohol by volume beer =1.7 units; 125 mL of 12 % wine =1.5 units: 50 mL of spirits with 40 % of alcohol by volume =2 units)
Subject tests positive for alcohol and/or drugs (urine tests) at Screening or Day -1
Subject has received any prescription (including hormonal replacement therapy) or nonprescription medicines, including over-the-counter (OTC) remedies, herbal, and dietary supplements (other than vitamins within recommended daily dose limits), within 21 days or 5 half-lives of the respective drug, whichever is longer, prior to Check-in (Day -1), other than occasional use of analgesics such as paracetamol (acetaminophen), ibuprofen, or intranasal corticosteroids for seasonal rhinitis
Subject has consumed any grapefruit, grapefruit juice, or grapefruit-containing products, as well as St John's Wort-containing products, within 14 days prior to Check-in (Day -1)
Subject has a known hypersensitivity to any components of the IMP
Subject has current or past history of GI ulceration
Subject is considered anti-immunoglobulin E (IgE) nonresponsive if CD63 induction on basophils is <10 %.
Subject has cardiovascular or cerebrovascular disease, including hypertension, angina, ischemic heart disease, transient ischemic attacks, stroke, and peripheral arterial disease sufficient to cause symptoms and/ or require therapy to maintain stable status
Subject has diabetes mellitus of any type requiring insulin
Subject has unstable/poorly controlled Type 2 diabetes mellitus, defined as glycosylated hemoglobin type A1c (HbA1c) level ≥8.5 % or glucose intolerant
Subject
Subject has a history of positive tuberculosis (TB) test or evidence of possible TB or latent TB infection at Screening (interferon gamma release assay [IGRA] testing)
Subject has received live attenuated vaccination within 3 months or any other type of vaccine within 4 weeks prior to Screening or intends to have such a vaccination during the course of the study
Subject who has any of the following hematology values at Screening:
Subject has an abnormality in the 12-lead ECG that, in the opinion of the Investigator, increases the risks associated with participating in the study. In addition any subject with any of the following findings will be excluded:
Subject has active neoplastic disease or history of neoplastic disease within 5 years of Screening (except for basal or squamous cell carcinoma of the skin or carcinoma in situ that has been definitively treated with standard of care)
Subject has any other acute or chronic illness which, in the opinion of the Investigator or the Sponsor's Study Physician, could pose a threat or harm to the subject
Subject is legally institutionalized or has a mental health condition or related care provision (eg, guardianship) that would impede the subject from providing voluntary informed consent to participate in the study
Healthy subjects only
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| Name | Affiliation | Role |
|---|---|---|
| UCB, Cares | 1-877-822-9493 | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| 001 | Harrow | United Kingdom |
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| ID | Term |
|---|---|
| D011565 | Psoriasis |
| ID | Term |
|---|---|
| D017444 | Skin Diseases, Papulosquamous |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
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| UCB5857 Part 2 | Drug | Active substance: UCB5857 Pharmaceutical form: Capsule Concentration: 5 mg, 8 mg, 15 mg Route of administration: Oral |
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| Placebo | Other | Active substance: Placebo Pharmaceutical form: Capsule Concentration: Avicel PH 102, 50 mg Route of administration: Oral |
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| Pharmacokinetic samples will be taken predose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 24, 48 and 72 hours postdose on Day 1 (Part 1 and Part 2) |
| The area under the plasma concentration-time curve from time 0 to infinity (AUC) | Pharmacokinetic samples will be taken predose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 24, 48 and 72 hours postdose on Day 1 (Part 1 and Part 2) |
| The maximum observed plasma concentration of UCB5857 after single dosing, obtained directly from the observed plasma concentration-time curves (Cmax) | Pharmacokinetic samples will be taken predose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 24, 48 and 72 hours postdose on Day 1 (Part 1 and Part 2) |
| The time of occurrence of Cmax, obtained directly from the observed plasma concentration-time curves (tmax) | Pharmacokinetic samples will be taken predose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 24, 48 and 72 hours postdose on Day 1 (Part 1 and Part 2) |
| The apparent terminal half-life (t1/2) | Pharmacokinetic samples will be taken predose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 24, 48 and 72 hours postdose on Day 1 (Part 1 and Part 2) |
| The terminal elimination rate constant in plasma (λz) | Pharmacokinetic samples will be taken predose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 24, 48 and 72 hours postdose on Day 1 (Part 1 and Part 2) |
| The apparent volume of distribution after single dosing (Vz/F) | Pharmacokinetic samples will be taken predose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 24, 48 and 72 hours postdose on Day 1 (Part 1 and Part 2) |
| The apparent total body clearance after single dosing (CL/F) | Pharmacokinetic samples will be taken predose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 24, 48 and 72 hours postdose on Day 1 (Part 1 and Part 2) |
| Mean residence time (MRT) | Pharmacokinetic samples will be taken predose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 24, 48 and 72 hours postdose on Day 1 (Part 1 and Part 2) |
| Area under the plasma concentration-time curve from time 0 to the last quantifiable concentration (AUC(0-t)) | Pharmacokinetic samples will be taken predose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 24, 48 and 72 hours postdose on Day 14 (Part 2) |
| Area under the plasma concentration-time curve from time 0 to 24 hours (AUC(0-24)) | Pharmacokinetic samples will be taken predose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 24, 48 and 72 hours postdose on Day 14 (Part 2) |
| The time of occurrence of Cmax, obtained directly from the observed plasma concentration-time curves (tmax) | Pharmacokinetic samples will be taken predose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 24, 48 and 72 hours postdose on Day 14 (Part 2) |
| The apparent terminal half-life (t1/2) | Pharmacokinetic samples will be taken predose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 24, 48 and 72 hours postdose on Day 14 (Part 2) |
| The terminal elimination rate constant in plasma (λz) | Pharmacokinetic samples will be taken predose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 24, 48 and 72 hours postdose on Day 14 (Part 2) |
| Mean residence time (MRT) | Pharmacokinetic samples will be taken predose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 24, 48 and 72 hours postdose on Day 14 (Part 2) |
| The maximum observed plasma concentration of UCB5857 during steady state, obtained directly from the observed plasma concentration-time curves (Cmaxss) | Pharmacokinetic samples will be taken predose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 24, 48 and 72 hours postdose on Day 14 (Part 2) |
| The minimum observed plasma concentration of UCB5857 during steady state immediately before the next dose would be administered, obtained directly from the observed plasma concentration-time curves (Ctrough) | Pharmacokinetic samples will be taken predose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 24, 48 and 72 hours postdose on Day 14 (Part 2) |
| The apparent volume of distribution at steady state (Vzss/F) | Pharmacokinetic samples will be taken predose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 24, 48 and 72 hours postdose on Day 14 (Part 2) |
| The apparent total body clearance at steady state (CLss/F) | Pharmacokinetic samples will be taken predose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 24, 48 and 72 hours postdose on Day 14 (Part 2) |
| Accumulation factor based on AUC(0-24) (RAUC) | Pharmacokinetic samples will be taken predose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 24, 48 and 72 hours postdose on Day 14 (Part 2) |
| Accumulation factor based on Cmax (R(Cmax)) | Pharmacokinetic samples will be taken predose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 24, 48 and 72 hours postdose on Day 14 (Part 2) |
| Time independency factor (TI) | Pharmacokinetic samples will be taken predose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 24, 48 and 72 hours postdose on Day 14 (Part 2) |
| Total amount of drug excreted in urine from time 0 to time t (Ae(0-t)) | Urine pharmacokinetic samples will be taken predose and 0 - 5 hours, 5 - 10 hours, 10 - 24 hours, 24 - 48 hours, 48 - 72 hours postdose on Day 1 (Part 1 and Part 2) and on Day 14 (Part 2) |
| Renal clearance (CLr) | Urine pharmacokinetic samples will be taken predose and 0 - 5 hours, 5 - 10 hours, 10 - 24 hours, 24 - 48 hours, 48 - 72 hours postdose on Day 1 (Part 1 and Part 2) and on Day 14 (Part 2) |
| Fraction of drug excreted in urine (Fe) | Urine pharmacokinetic samples will be taken predose and 0 - 5 hours, 5 - 10 hours, 10 - 24 hours, 24 - 48 hours, 48 - 72 hours postdose on Day 1 (Part 1 and Part 2) and on Day 14 (Part 2) |
| Basophil degranulation | Samples will be taken predose, 0.5, 1, 2, 4, 6, 8, 10, 24 hours postdose on Day 1 (Part 1 and Part 2) and predose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 hours postdose on Day 14 (Part 2) |