Safety and Pharmacokinetics of Hemay005 In Healthy Male Subjects

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

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.

Study Overview

• Status: Completed
• Conditions: Psoriasis
• Intervention / Treatment: Drug: Hemay005; Drug: Placebos

• Study Type: Interventional
• Enrollment (Actual): 68
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijin, China
    • Peking Union Medical College Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. Male subjects aged 18 to 60 years;
2. Bodyweight（BW）≥ 50kg, Body mass index (BMI) in 18-28 (including upper and lower limit of the range);
3. 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);
4. Ability to understand and be willing to sign a written informed consent before study entry;
5. Subjects would have good communication with the investigator and could comply with protocol.

Exclusion Criteria:

1. A history of clinically severe gastrointestinal, hepatic, renal, cardiovascular, dermatological, immunological, respiratory, endocrine, oncological, neurological, metabolic, psychiatric disease or haematological disorders;
2. 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;
3. Have a gastrointestinal, hepatic or renal condition that may influence drug absorption or metabolism;
4. A history of chronic infection (ie, tuberculosis);
5. A medical history of any clinically significant medical disease or surgery within 4 weeks of the screening;
6. Clinically significant laboratory abnormal results at screening or prior to the first dose of study drug;
7. 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);
8. Positive blood screen for human immunodeficiency virus (HIV antibody), hepatitis B virus surface antigen, or hepatitis C virus antibody at screening;
9. 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;
10. Positive urine screen for drug and cigarettes, positive breath test for alcohol;
11. 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;
12. Dietary habits or food intolerances which will interfere with the requirements for participants to consume a standardised diet whilst confined to the clinical unit;
13. 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;
14. 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);
15. Participant who received any medicine within 14 days of the initial dose of study drug;
16. Have received other clinical trials treatment within 3 months prior to study;
17. 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;
18. Subjects cannot complete the study due to other reasons or by the investigator's judgment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Tianjin Hemay Bio-Tech Co., Ltd

Study record dates

Study Major Dates

• Study Start: December 1, 2016
• Primary Completion (ACTUAL): June 1, 2018
• Study Completion (ACTUAL): June 1, 2018

Study Registration Dates

• First Submitted: December 22, 2016
• First Submitted That Met QC Criteria: December 29, 2016
• First Posted (ESTIMATE): January 2, 2017

Study Record Updates

• Last Update Posted (ACTUAL): June 19, 2018
• Last Update Submitted That Met QC Criteria: June 17, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Skin Diseases, Papulosquamous; Psoriasis; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Dermatologic Agents; Phosphodiesterase Inhibitors; Phosphodiesterase 4 Inhibitors; Hemay005
• Other Study ID Numbers: HM005PS1S01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO