Multiple Ascending Doses of SY-008 in Type 2 Diabetes Mellitus

NCT04345120 | Completed Phase 1

• 1 other identifier: SY008002
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase Ib placebo-controlled study to assess safety, tolerability, pharmacokinetics and pharmacodynamics of SY-008 after Multiple Ascending Doses in patients with Type 2 Diabetes Mellitus (T2DM).

Conditions

Type 2 Diabetes Mellitus

Outcome Measures

Primary Outcomes (7)

• Maximum postprandial (breakfast, lunch, dinner) blood glucose added value.

  Compared with placebo, the maximum change in glucose from baseline at D7.

  7 days

• Blood glucose AUC (AUC 0-4,AUC 4-10, AUC 10-14, AUC 0-24) in different periods.

  Compared with placebo, the mean change in glucose AUC from baseline at D7.

  7 days

• The Safety and tolerance of SY-009，Collecting Number of subjects with adverse events as assessed by CTCAE V5.0.

  Number of subjects with adverse events, major adverse events, serious adverse events, abnormal Laboratory Values, abnormal vital signs, Abnormal physical examination, Abnormal ECG data，Gastrointestinal adverse reactions (diarrhea, etc.) and hypoglycemia events.

  7 days

• C-peptide concentration changes before and after meal.

  Compared with placebo, the mean change from baseline at D7.

  7 days

• The changes of insulin concentration before and after meal.

  Compared with placebo, the mean change from baseline at D7.

  7 days

• GLP-1 concentration changes before and after meal.

  Compared with placebo, the mean change from baseline at D7.

  7 days

• GIP concentration changes before and after meal.

  Compared with placebo, the mean change from baseline at D7.

  7 days

Secondary Outcomes (17)

• Peak concentration (Cmax)

  1 day

• Peak time (Tmax)

  1 day

• Terminal elimination rate constant (λ z)

  1 day

• Terminal elimination half-life (T1 / 2)

  1 day

• Area under the drug time curve from 0 to the last detectable time (auc0-t)

  1 day

Study Arms (4)

SY-008-6mg/d

EXPERIMENTAL

2mg TID. The subjects were given the drug for the first time before breakfast in D1, and then continued to take the drug daily until dinner in D7, and left after PD sample collection and safety assessment before breakfast in D8. The researchers will decide whether to move on to the next stage，12mg/d.

Drug: SY-008

SY-008-12mg/d

EXPERIMENTAL

4mg TID. The subjects were given the drug for the first time before breakfast in D1, and then continued to take the drug daily until dinner in D7, and left after PD sample collection and safety assessment before breakfast in D8. The researchers will decide whether to move on to the next stage，18mg/d.

Drug: SY-008

SY-008-18mg/d

EXPERIMENTAL

6mg TID. The subjects were given the drug for the first time before breakfast in D1, and then continued to take the drug daily until dinner in D7, and left after PD sample collection and safety assessment before breakfast in D8, and then the test will be terminated.

Drug: SY-008

SY-008 matching placebo

PLACEBO COMPARATOR

Oral administration of the same number of tablets in the corresponding test group.

Drug: SY-008 matching placebo

Interventions

SY-008 DRUG

The subjects were admitted to the clinical trial center two days before the administration period (D-2), fasted for 10 hours overnight on the day before the Administration (D-1), and banned water for 1 hour before the administration. Take sy-009 test drug or placebo immediately before meal (QD is before breakfast, bid is before breakfast and dinner) in the morning of the first day of administration, and deliver it with not more than 200ml warm boiled water. From the day 2 (D2) to the day 7 (D7) before dinner, the oral cavity of the subjects was checked for residual drugs after each administration.

SY-008-12mg/d; SY-008-18mg/d; SY-008-6mg/d

SY-008 matching placebo DRUG

SY-008 matching placebo

SY-008 matching placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• body weight of male ≥ 50kg, female ≥ 45kg, and body mass index (BMI) between 18.0 and 35.0 kg / m2 (including the threshold value) at screening;
• Have T2DM prior to entering the trial based on the disease diagnostic criteria (WHO, 1999), and currently being treated with diet and exercise only for at last 12 weeks , or no systemic treatment of diabetes (the cumulative use of antidiabetic drugs in the past 3 months has lasted no more than 2 weeks and no antidiabetic drugs has been used in the past month);
• % ≤ HbA1c ≤ 9.5% at screening;
• mmol/L≤FPG ≤ 13.3 mmol/L at baseline;
• During the study period and within 60 days after the end of the study, the subjects has no fertility or sperm / egg donation plan and will voluntarily take effective physical contraceptive measures;
• Have given written informed consent to participate in this study, are well motivated, capable, and willing to communicate with the investigator and complete all the requirements according to the protocol.

You may not qualify if:

• Those who are known to be allergic to the test drug (including the auxiliary materials of the test drug) or its analogues, or who are allergic to two or more drugs, food and pollen, or who have taken SGLT1 or SGLT2 inhibitors in the past year;
• It was diagnosed as type 1 diabetes, or gestational diabetes, or other special type diabetes;
• There is enough evidence to show that there is proliferative retinopathy of active diabetes;
• History of severe hypoglycemia (such as consciousness disorder and coma caused by hypoglycemia), or history of severe unconsciousness hypoglycemia;
• Organ transplantation history, or other acquired, congenital immune system diseases, or peripheral vascular diseases with clinical significance;
• Have significant hyperglycemia symptoms, such as polyuria, polydipsia, accidental weight loss or dehydration;
• Habitual diarrhea, irritable bowel syndrome, clinically significant abnormal gastric emptying (such as gastric outlet obstruction), severe chronic gastrointestinal diseases (such as active ulcer within 6 months), long-term medication with direct impact on gastrointestinal peristalsis, or gastrointestinal surgery;
• Have obvious blood system diseases (such as aplastic anemia, myelodysplastic syndrome), or any disease causing hemolysis or red blood cell instability (such as malaria), or accompanied by hemoglobin diseases (such as sickle type red blood cell disease) that may affect the determination of HbA1c level;
• Obvious autonomic neuropathy, such as urinary retention, orthostatic hypotension, diabetic diarrhea or gastroparesis.
• History of heart failure (NYHA class Ⅲ and Ⅳ, Appendix 2), or history of acute myocardial infarction or unstable angina within 6 months before screening, or history of coronary angioplasty, coronary stent implantation or coronary bypass surgery within 6 months before screening, or recent cardiac surgery plan;
• Serious trauma, infection or operation that may affect blood glucose control occurred within one month before screening;
• In the first two months of the screening, the drug with weight control effect was used or the operation that can lead to weight instability was performed, or the drug is currently in the weight-loss plan and is not in the maintenance stage;
• Completed or withdrawn an intervention clinical trial within 3 months before screening, or is currently conducting the intervention clinical trial, or participated in other medical research activities, which is not suitable for the study according to the judgment of the researcher;
• Those who frequently drink alcohol (more than 21 units (male) and 14 units / week (female) (1 unit = 360ml beer; or 150ml wine; or 45ml white wine) in the three months before screening, or who can't stop drinking during the test;
• Those who are addicted to smoking (more than 10 cigarettes per day or the same amount of tobacco) within 3 months before screening or who cannot quit smoking (stop nicotine intake) during the trial;

Sponsors & Collaborators

• Suzhou Yabao Pharmaceutical R&D Co., Ltd.: lead

Study Sites (1)

Nanjing Gulou Hospital

Nanjing, Jiangsu, 210093, China

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 9, 2020
• First Posted: April 14, 2020
• Study Start: June 15, 2020
• Primary Completion: December 15, 2021
• Study Completion: December 15, 2021
• Last Updated: May 18, 2022

Record last verified: 2021-05

Locations

CN (1)