Multiple Ascending Doses of Globalagliatin Hydrochloride in Type 2 Diabetes Mellitus

NCT03414892 | Completed Phase 1

• 1 other identifier: YB17071
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase I placebo-controlled study to assess safety, tolerability, pharmacokinetics and pharmacodynamics of Globalagliatin Hydrochloride (SY-004) after Multiple Ascending Doses in patients with Type 2 Diabetes Mellitus (T2DM).

Conditions

Hyperglycaemia (Diabetic); Type 2 Diabetes Mellitus

Keywords

Type 2 Diabetes Mellitus; Glucokinase Activator

Outcome Measures

Primary Outcomes (1)

• the mean change in glucose area under curve (AUC) from baseline.

  Compared with placebo, the mean change in glucose AUC from baseline at D28.

  28 days

Secondary Outcomes (5)

• the fasting plasma glucose from baseline

  7, 14, 21, 28 days

• the changes of MMTT (mixed-meal tolerance test) results from baseline

  28 days

• the mean changes of average 7-points blood glucose profiles from baseline

  7, 14, 21, 28 days

• the mean changes of average 14-points blood glucose profiles from baseline

  7, 14, 21, 28 days

• the mean changes of post-prandial blood glucose from baseline

  7, 14, 21, 28 days

Other Outcomes (2)

• genetic: TCF7L2 ( Transcription factor 7-like 2) rs7903146 and GCKR (glucokinase regulatory protein) rs780094 )

  28 days

• the changes of GA (Glycated albumin) from baseline

  28 days

Study Arms (2)

Globalagliatin Hydrochloride (SY-004)

EXPERIMENTAL

If subjects tolerate 20mg of Globalagliatin Hydrochloride (SY-004) for 7 days, dose escalation will occur in the following order of 40mg, 80mg and 120mg at weekly intervals until patients get intolerant or blood glucose controlled well or reach the maximal dose 120mg.

Drug: Globalagliatin Hydrochloride

Placebo

PLACEBO COMPARATOR

If subjects tolerate 20mg of Placebo for 7 days, dose escalation will occur in the following order of 40mg, 80mg and 120mg at weekly intervals until patients get intolerant or blood glucose controlled well or reach the maximal dose 120mg.

Drug: Placebo

Interventions

Globalagliatin Hydrochloride DRUG

once daily, oral

Also known as: SY-004

Globalagliatin Hydrochloride (SY-004)

Placebo DRUG

once daily, oral

Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Sex：Male and Female；
• Age：≥18，≤70；
• Have T2DM prior to entering the trial based on the disease diagnostic criteria (WHO, 1999), and currently being treated with diet and exercise only or in combined with a stable dose of metformin for at least 8 weeks.
• kg/m2≤BMI≤35 kg/m2 at screening.
• % ≤ HbA1c ≤11% at screening.
• mmol/L≤FPG≤13.3mmol/L at baseline.
• The venous access is normal, and blood samples can be collected according to the protocol.
• 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:

• Personnel and their direct relatives of the clinical research unit and its related facilities. Direct relatives mean all biologically and by law related relatives, including spouse, parent, child and sibling,
• Have been diagnosed with type 1 diabetes, or gestational diabetes mellitus, or a specific type of diabetes mellitus.
• Clinically significant coronary events or symptoms within 6 months prior to study entry.
• Clinically significant peripheral vascular disease.
• Clinical evidence of active diabetic proliferative retinopathy.
• Known clinically significant autonomic neuropathy as evidenced by urinary retention, orthostatic hypotension, diabetic diarrhea or gastroparesis.
• With a history of diabetes or diabetic ketoacidosis, lactic acidosis, hyperosmolar nonketotic coma history.
• Have severe hypoglycemia occurred before the screening with unknown causes (need other people to help restore) or the frequency of hypoglycemia, such as 3 or more hypoglycemic events(blood glucose ≤3.9mmol/L) within 1 months before screening or hypoglycemia related symptoms.
• Continuous use of insulin for more than 1 month in last year.
• Have any disorder or unstable situation of the endocrine system, immune system or other diseases impaired blood sugar(such as Hyperthyroidism, acromegaly, Cushing syndrome) that are required treatment
• Have significant history of past or current cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine (other than diabetes), hematological, or neurological disorders capable of significantly altering the absorption, metabolism or elimination of drugs or of constituting a risk when taking the study drug formulations or interfering with the interpretation of data.
• Have any types of malignancies (whether cured or not).
• History of haemoglobin disease（such as sickle cell anemia or thalassemia, iron deficiency anemia）.
• Have known allergies to Globalagliatin or related compounds, or have allergic history, or have taken glucokinase activator in last year.
• Are currently enrolled in, or discontinued within the last 3 months from, a clinical trial involving an investigational drug or device or use of a drug or device other than the study drug used in this study, or are concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study.

Sponsors & Collaborators

• Yabao Pharmaceutical Group: lead

Study Sites (1)

The First Affiliated Hospital of Nanjing Medical University

Nanjing, Jiangsu, China

Location

Related Publications (1)

• Zheng S, Shao F, Ding Y, Fu Z, Fu Q, Ding S, Xie L, Chen J, Zhou S, Zhang H, Zhou H, Chen Y, Sun C, Zhu J, Zheng X, Yang T. Safety, Pharmacokinetics, and Pharmacodynamics of Globalagliatin, a Glucokinase Activator, in Chinese Patients with Type 2 Diabetes Mellitus: A Randomized, Phase Ib, 28-day Ascending Dose Study. Clin Drug Investig. 2020 Dec;40(12):1155-1166. doi: 10.1007/s40261-020-00971-x. Epub 2020 Oct 30.

  PMID: 33125674 DERIVED

MeSH Terms

Conditions

Hyperglycemia; Diabetes Mellitus, Type 2

Condition Hierarchy (Ancestors)

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

Study Officials

• Lei Yang

  Yabao pharmaceutical Group Co.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 7, 2018
• First Posted: January 30, 2018
• Study Start: January 3, 2018
• Primary Completion: January 4, 2019
• Study Completion: December 1, 2019
• Last Updated: January 3, 2020

Record last verified: 2018-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)