Clinical trial NCT03462589: Single Ascending Oral Doses of SY-008 in Healthy Subjects
Official title: Randomized, Double-blind, Placebo-controlled, Dose Escalated Tolerance and Pharmacokinetic / Pharmacodynamic Studies of SY-008 Capsules Administered by Chinese Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Diabetes
Lead sponsor: Suzhou Yabao Pharmaceutical R&D Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2018-03-12
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a phase Ⅰ，single-center, randomized, double-blinded, placebo-controlled, single ascending dose trial of SY-008 in healthy subjects.

Detailed description: This is a randomized, double-blind, placebo-controlled, dosed tolerability, pharmacokinetic / pharmacodynamic study of a single oral SY-008 capsule for Chinese healthy subjects. Plan to screening total of 54 healthy subjects ， dividing them into 6 dose groups.

Eligibility criteria: Inclusion Criteria:

1. Gender: Male and female, gender balance.
2. Age: 18-65 years old (including the boundary values).
3. Weight ≥50kg and 19kg / m2 ≤ BMI ≤ 28kg / m2 \[BMI = body weight (kg) / height 2 (m2).
4. fasting plasm glucose (FPG): 3.9-6.1mmol / L (excluding the boundary values).
5. glycosylated hemoglobin (HbA1c) \<6.5%.
6. healthy subjects determined by medical history, physical examination, electrocardiogram and laboratory tests. Test results within the normal range for the population or investigator site, or with abnormalities deemed clinically insignificant by the investigator.
7. have venous access sufficient to allow blood sampling as per the protocol.
8. have given written informed consent approved by sponsors and the ethical review board governing the site.
9. are reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures.

Exclusion Criteria:

1. are investigator site personnel directly affiliated with this study and their immediate families. Immediate family is defined as a spouse, parent, child or sibling, whether biological or legally adopted.
2. within 3 months prior to screening, complete or withdraw a clinical study, or are currently conducting a clinical study. Or are concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study.
3. have previously completed or withdrawn from this study.
4. 2h postprandial plasm glucose (2hPPG) ≥7.8 mmol / L（Test on -1 Day）.
5. have known allergies to compounds related to SY-008 capsules or multiple drug allergies, or have been treated with SGLT-1(sodium-glucose cotransporter-1) inhibitors in 1 year.
6. have significant history of or current cardiovascular, respiratory, hepatic, renal, gastrointestinal (such as hemorrhoids, inflammation of GI tract, tumor, history of surgery, habitual bellyache or diarrheal disorders, other motility disorders), endocrine, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs or of constituting a risk when taking the study medication or interfering with the interpretation of data.
7. have a history of alcohol abuse or drug abuse.
8. show evidence or test positive on any of the following: hepatitis B virus surface antigen (HBsAg), hepatitis C virus antibody (HCV), Treponema pallidum antibody (TP), HIV (HIV1 + 2) antibody.
9. have donated blood of 400 mL or more in the last 3 months or provided any blood donation within the last month from screening.
10. are subjects who have an average weekly alcohol intake that exceeds 21 units per week (males) and 14 units per week (females; 1 unit = 12 oz or 360 mL of beer; 5 oz or 150 mL of wine; 1.5 oz or 45 mL of distilled spirits) or are subjects unwilling to stop alcohol consumption 24 hours prior to dosing until the completion of each inpatient study period.
11. consume more than 10 cigarettes per day or the equivalent, or are unable or unwilling to refrain from nicotine during the study.
12. intend to use over-the-counter or prescription medications within 14 days prior to dosing or during the study.
13. subjects not agree to use reliable contraceptive methods (hormones or barriers or abstinence) during the study period and at least 1 month after administration.
14. women were positive for blood pregnancy test within 24 hours prior to enrollment.
15. pregnant or lactating women.
16. in the opinion of the investigator or sponsor, are unsuitable for inclusion in the study.

Primary outcomes:
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.03
timeFrame: 7 days
Secondary outcomes:
measure: area under curve (AUC) of SY-008 following oral administration of single ascending dose
timeFrame: 3 days
measure: Cmax of SY-008 following oral administration of single ascending dose
timeFrame: 3 days
measure: T1/2 of SY-008 following oral administration of single ascending dose
timeFrame: 3 days
measure: CL/F (Clearance rectified) of SY-008 following oral administration of single ascending dose
timeFrame: 3 days
measure: glucose levels following single dose of SY-008
timeFrame: 24 hours
measure: insulin secretion following single dose of SY-008
timeFrame: 3 days
measure: C-peptide secretion following single dose of SY-008
timeFrame: 6 hours
Other outcomes:
Locations:
city: Nanjing
country: China
facility: The First Affiliated Hospital of Nanjing Medical University
state: Jiangsu
Study officials:
affiliation: The Frist Affiliated Hospital Of Nanjing Madical University
name: Feng Shao, Doctor
role: PRINCIPAL_INVESTIGATOR
References: