Clinical trial NCT03655873: The Study of a Selective 5-ht6 Receptor Antagonist, HEC30654AcOH,in Healthy Subjects
Official title: Safety, Tolerability, and Pharmacokinetics Phase ⅠStudy of a Selective 5-ht6 Receptor Antagonist, HEC30654AcOH, Following Single and Multiple Ascending Doses，Single-center, Randomized, Double-blind in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Sunshine Lake Pharma Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2018-08-31
Enrollment: 99
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: This study is a safety, tolerability, and pharmacokinetics phase Ⅰstudy of a selective 5-ht6 receptor antagonist, HEC30654AcOH,in healthy subjects.This test is divided into two parts, the first part is the healthy adult subjects single ascending-dose research;The second part is the healthy adult subjects multiple ascending-dose research.

Detailed description: The single ascending-dose research:

There have set up seven dose group(5、10、15、30、60、90、120mg）.The first group(5mg)contains 3 health subjects，Which have been a preliminary experimental group. Each other groups contains 10 health subjects(8 health subjects take experimental drugs,2 health subjects take the placebo).Within 15min before taking the medicine and after 0.5h, 1h, 1.5h, 2h, 4h, 6h, 8h, 10h, 12h, 24h, 48h, 72h, 96h, 120h to take blood samples for pharmacokinetics(PK) detection.

The multiple ascending-dose research:

There have set up three dose group(15、30、60mg）.Each group contains 12 health subjects(10 health subjects take experimental drugs,2 health subjects take the placebo).Each dose group in D1-D7 8:00（±1h）in the morning, 18:00（±1h）, with 240 ml warm water to take corresponding study drug，but Day 8 only 8:00（±1h） in the morning take subjects drugs.Total for 15 times.on the morning of day 1 within 15minutes before the first drug and after 0.5h, 1h, 1.5h, 2h, 4h, 6h, 8h, 10h, 12h, on the morning of Day 6, Day 7 and Day 8 within 15 minutes before the drug collecting blood sample test concentration, on the morning of Day8 medication after 0.5h 1h, 1.5h, 2h, 4h, 6h, 8h, 10h, 12h, 24h, 48h, 72h, 96h, 120h collects pharmacokinetics(PK) blood samples.

Eligibility criteria: Inclusion Criteria:

* signing informed consent, and fully understanding the study's content, process，possible adverse reaction before the study beginning.
* Be able to complete the study in accordance with the requirements of the study.
* Subjects (including partner) which from screening to the last time of study drug dosage volunteered to take effective contraceptive measures within 6 months, see appendix for birth control measures.
* Age of 18 to 45 years old male and female subjects (including 18 and 45 years of age).
* Male subjects not less than 50 kg, female subjects not less than 45 kg weight.Body mass index (BMI) = weight (kg)/height 2 (m2), body mass index (BMI) within the scope of 18 \~ 28 kg/m2 (including threshold).
* Physical examination, vital signs is normal or abnormal has no clinical significance.

Exclusion Criteria:

* 3 months before the study daily smoking more than 5 pieces.
* having allergies or allergic constitution for experiment drugs (a variety of drugs and food allergies).
* Has a history of drug and/or binge drinking (drinking 14 units of alcohol every week: 1 unit = 285 mL beer, or liquor 25 mL, or wine 100 mL).
* Three months before screening blood or blood loss (\> 450 mL).
* 28 days before the screening taking any drugs of changing liver enzymes.
* Within 14 days before the screening taken any prescription drugs, over-the-counter drugs, vitamins or herbal products.
* Within 2 weeks before the screening taking any special diet (including dragon fruit, mango, pomelo, etc.) or with vigorous exercise, or other affect drug absorption, distribution, metabolism and excretion.
* With the following CYP3A4, P - gp or Bcrp inhibitors or inducers, such as itraconazole, ketone health zun or definitely nida, lung, etc.
* Recently, very large changes in diet or exercise habits.
* Three months before taking study drug, there taken study drug and its analogues, or participated in drug clinical trials.
* Having difficulty swallowing or any digestive system diseases history affecting drug absorption, excretion,etc.
* Having had any increased risk of hemorrhagic disease, such as hemorrhoids, acute gastritis or gastric and duodenal ulcer, etc.
* Abnormal ecg that have clinical significance.
* Female subjects in screening test is in lactation or have positive serum pregnancy outcomes.
* Clinical laboratory examination were abnormal clinical significance, or other clinical findings show that there are clinical significance of the following diseases (including but not limited to the gastrointestinal tract, liver, kidney, and nerve, blood, endocrine, tumor, lung, immune, spirit, or disease of heart head blood-vessel).
* Viral hepatitis (including hepatitis b and c),, treponema pallidum antibody , HIV antibody positive.
* From the screening stage to study medicine had a acute disease or taken a drugs.
* Within 48 hours before taking the study drug, there taken any caffeine consumed chocolate, or rich xanthine food or drinks.
* Within 24 hours before taking study drug, there used any alcoholic products or alcohol-breath test was positive.
* Urine drug test(Morphine and marijuana) was positive.
* Neurological examination had abnormal findings, and researchers think have clinical significance.
* Researchers think that doesn't fit to the study.

Primary outcomes:
measure: Adverse events of the single ascending-dose
timeFrame: From the baseline to 6 days
measure: Adverse events of the multiple ascending-dose
timeFrame: From the baseline to 13 days
Secondary outcomes:
measure: Maximum Plasma Concentration(Cmax)
timeFrame: Prior to dosing（0h）and 0.5h,1h,1.5h,2h,4h,6h,8h,10h,12h,24h,48h,72h,96h,120h after dosing
measure: Area Under the Curve(AUC)
timeFrame: Prior to dosing（0h）and 0.5h,1h,1.5h,2h,4h,6h,8h,10h,12h,24h,48h,72h,96h,120h after dosing
measure: Maximum Peak Time(Tmax)
timeFrame: Prior to dosing（0h）and 0.5h,1h,1.5h,2h,4h,6h,8h,10h,12h,24h,48h,72h,96h,120h after dosing
measure: Mean Residence Time(MRT)
timeFrame: Prior to dosing（0h）and 0.5h,1h,1.5h,2h,4h,6h,8h,10h,12h,24h,48h,72h,96h,120h after dosing
measure: Terminal elimination half-life(T1/2)
timeFrame: Prior to dosing（0h）and 0.5h,1h,1.5h,2h,4h,6h,8h,10h,12h,24h,48h,72h,96h,120h after dosing
measure: steady state plasma concentration(Css）
timeFrame: Prior to dosing（0h）and 0.5h,1h,1.5h,2h,4h,6h,8h,10h,12h after dosing day1,then Prior to dosing（0h）of day6，day7,day8，and 0.5h，1h，1.5h，2h，4h，6h，8h，10h，12h，24h，48h，72h，96h，120h after dosing day8
Other outcomes:
Locations:
city: Changchun
country: China
facility: First Hospital of Jilin University
state: Jilin
Study officials:
References: