Safety and Pharmacokinetics of Hemay005 In Healthy Male Subjects

Study Overview
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Brief Summary
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Hemay005 is a novel phosphodiesterase type 4(PDE4) inhibitor being developed for the treatment of psoriasis. This study is the first administration of Hemay005 in humans to establish the initial safety, tolerability, and pharmacokinetic profile following single doses of Hemay005. A total of approximately 44 subjects will be randomized into 6 cohorts(10mg, 20mg, 40mg, 80mg, 120mg, 180mg), approximately 8 healthy subjects will be enrolled (6 active and 2 placebo) at each dose cohort by sentinel method(1 active and 1 placebo,5 active and 1 placebo), with the exception of 10mg (4 active) cohort. This study includes an 28-day Screening Period, a 1-day Treatment Period, and an End of Study Visit occurring approximately 11days (±3 days) after study drug administration.

Official Title
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An Ascending Single Dose Study of the Pharmacokinetics, Safety and Tolerability of Hemay005 in Healthy Male Subjects

Conditions
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Psoriasis

Intervention / Treatment
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* Drug: Hemay005
* Drug: Placebos


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male subjects aged 18 to 60 years; Bodyweight（BW）≥ 50kg, Body mass index (BMI) in 18-28 (including upper and lower limit of the range); All male subjects must agree and commit to the use of a reliable contraceptive regimen(including vasoligation, abstinence, using a condom) for the duration of the study(from screening until 6 months after the last dose); Ability to understand and be willing to sign a written informed consent before study entry; Subjects would have good communication with the investigator and could comply with protocol. Exclusion Criteria: A history of clinically severe gastrointestinal, hepatic, renal, cardiovascular, dermatological, immunological, respiratory, endocrine, oncological, neurological, metabolic, psychiatric disease or haematological disorders; Have a known history of hypersensitivity to any medicine or food, or allergy to the test article or any of the excipient of the test article; Have a gastrointestinal, hepatic or renal condition that may influence drug absorption or metabolism; A history of chronic infection (ie, tuberculosis); A medical history of any clinically significant medical disease or surgery within 4 weeks of the screening; Clinically significant laboratory abnormal results at screening or prior to the first dose of study drug; Clinically significant abnormal 12-lead ECG or vital signs ( systolic pressure <90 mmHg or >140 mmHg, diastolic pressure <50 mmHg or >90 mmHg; radial pulse rate <50 bpm or >100 bpm); Positive blood screen for human immunodeficiency virus (HIV antibody), hepatitis B virus surface antigen, or hepatitis C virus antibody at screening; Recent history of frequent alcohol consumption, defined by average intake of greater than 14 units of alcohol per week (1 unit = 360 mL beer or 45 mL of spirits with 40% alcohol content, or 150 mL wine), Participants who are unable to abstain from smoking during the study or quitting smoking for less than 3 months; Positive urine screen for drug and cigarettes, positive breath test for alcohol; Subjects who use soft drugs (ie marijuana )within 3 months of the screening and entire study duration or hard drugs (ie cocaine, phencyclidine ) within 1 year of the screening and entire study duration; Dietary habits or food intolerances which will interfere with the requirements for participants to consume a standardised diet whilst confined to the clinical unit; Participants who eat special food (Including grapefruit and/or Xanthine diet) for 14 days prior to dosing or any caffeine containing food or drinks, i.e. chocolate for 48 hours prior to dosing or drinking alcohol for 24 hours prior to dosing and not will stop to intake above food and drinks; Use of any drug that inhibits or induces hepatic metabolism of drugs within 30 days of planned study drug administration and entire study duration (e.g. inducers: barbiturates, carbamazepine, rifampicin, phenytoin, glucocorticoid and omeprazole; inhibitors - SSRI antidepressants, cimetidine, diltiazem, macrolides, nitroimidazoles, sedatives and hypnotics, verapamil, fluoroquinolones and antihistamines); Participant who received any medicine within 14 days of the initial dose of study drug; Have received other clinical trials treatment within 3 months prior to study; Participants who have donated of blood (>400 mL) within 4 weeks of the study, or plan to donate of blood during of the study and 4 weeks after the study; Subjects cannot complete the study due to other reasons or by the investigator's judgment

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hemay005<br>Four subjects in cohort 1 and six subjects in each cohort (2 to 6) will receive Hemay005. | Drug: Hemay005<br>* Subjects will be randomized into 6 cohorts(10mg, 20mg, 40mg, 80mg, 120mg, 180mg) orally single dose<br>|
| Placebo Comparator: Placebo<br>Two subjects in each cohort (cohorts 2 to 6) will receive placebo. | Drug: Placebos<br>* Subjects will be randomized into 5 cohorts(20mg, 40mg, 80mg, 120mg, 180mg) orally single dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of adverse events and serious adverse events |  | Day 1 up to Day 11±3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax | Maximum observed plasma concentration | pre-dose, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48 hours post-dose | 
| Tmax | Time of maximum concentration | pre-dose, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48 hours post-dose | 
| AUCt | Area under the plasma concentration-time curve from time zero extrapolated to infinity | pre-dose, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48 hours post-dose | 
| AUC∞ | Area under the plasma concentration-time curve from time zero to the last quantifiable concentration | pre-dose, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48 hours post-dose | 
| t1/2 | Terminal elimination half-life | pre-dose, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48 hours post-dose | 
| CL/F | Apparent total plasma clearance | pre-dose, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48 hours post-dose | 
| Vz/F | Apparent total volume of distribution | pre-dose, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48 hours post-dose | 
| Cumulative urinary excretion |  | pre-dose, 0-4 hours，4-8 hours，8-12 hours，12-24 hours，24-36 hours，36-48 hours post-dose | 
| Accumulative urine excretion rate |  | pre-dose, 0-4 hours，4-8 hours，8-12 hours，12-24 hours，24-36 hours，36-48 hours post-dose | 
| Renal clearance |  | pre-dose, 0-4 hours，4-8 hours，8-12 hours，12-24 hours，24-36 hours，36-48 hours post-dose |