Hyperglycaemia (Diabetic)Phase 1NCT03414892
Multiple Ascending Doses of Globalagliatin Hydrochloride in Type 2 Diabetes Mellitus
A Phase 1 study testing Globalagliatin Hydrochloride in people with Hyperglycaemia (Diabetic) and Type 2 Diabetes Mellitus, run by Yabao Pharmaceutical Group at 1 site in China.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Hyperglycaemia (Diabetic), Type 2 Diabetes Mellitus
- What is being tested?
- Globalagliatin Hydrochloride
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 24 participants
- Where
- 1 siteChina
- Study dates
- 3 Jan 2018to 1 Dec 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
- 18 kg/m2≤BMI≤35 kg/m2 at screening.
- 7% ≤ HbA1c ≤11% at screening.
- 7 mmol/L≤FPG≤13.3mmol/L at baseline.
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- 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.
Who cannot join
- 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.
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- 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.
- Have a history of drug or alcohol abuse.
- Have history of blood donation in last 6 months.
- Patients who have an average weekly alcohol intake that exceeds 21 units per week (males) and 14 units per week (females) (1 unit = 360 mL of beer; 150 mL of wine; 45 mL of distilled spirits) or patients unwilling to stop alcohol consumption 24 hours prior to admission until the completion of each in-patient study period.
- Patients who smoke >10 cigarettes or other tobacco products per day before study entry. Patients are unlikely / unable to stop nicotine intake during the study period.
- Fasting serum C peptide< 1.0 ng/ml(333pmol/L)at screening.
- Patients are treated with stable dose of anti-hypertension drug at least for 4 weeks with inadequate blood pressure control (sitting systolic blood pressure≥160mmHg or diastolic blood pressure≥100mmHg)at screening.
- QTcB≥450msec at screening.
- Fasting serum triglycerides>500mg/dL(5.70mmol/L)at screening.
- ALT (alanine aminotransferase) >1.5 ULN, AST (aspartate transaminase) >1.5×ULN or TBIL (total bilirubin) > 1.5×ULN (UIN :times the upper limit of the reference range)at screening; or have active liver diseases at screening.
- Serum creatinine>133μmol /L at screening.
- Use of any known inducers or inhibitors of CYP3A (Cytochrome P450 3A) within 14 days prior to the first dosing with study drug or intended use during the study. Examples of inducers include, but are not limited to, phenytoin, barbiturates, carbamazepine, St. John's Wort, rifampin. Examples of inhibitors include, but are not limited to, fluvoxamine, sertraline, norfloxacin, macrolide antibiotics (erythromycin, clarithromycin), antifungals, human immunodeficiency virus (HIV) protease inhibitors, cyclosporine, diltiazem, pomelo, grapefruit juice.
- Have been previously enrolled in or withdrawn from this clinical trial.
- Evidence of positive HBsAg, or IgM (immunoglobulin M ) anti-HBc (hepatitis B core antigen), or anti-HCV (hepatitis C virus ), or anti-HIV, or anti-TPat (treponema pallidum antibody) screening.
- fertility qualified subjects(Male and Female)are unlikely to use reliable contraception during study period and at least 1 month after last dosing or women in child-bearing age have positive for blood pregnancy tests within 24 hours before enrollment, or pregnant or lactating women.
- Patients, in opinion of investigator or sponsor, are not suitable for this clinical trial.
Trial locations and contacts
1 site in 1 country.
China1 site
The First Affiliated Hospital of Nanjing Medical University
Nanjing, Jiangsu
About this study
Official title: A Phase I Placebo-controlled Study to Assess Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Globalagliatin Hydrochloride After Multiple Ascending Doses in Patients With Type 2 Diabetes Mellitus
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).
Read the detailed description
Glucokinase is a characteristic hexokinase isoenzyme in hepatocytes that catalyzes the first step in glucose metabolism. In addition to its role in glucose metabolism, glucokinase is expressed in pancreatic islet beta cells where it acts as a "glucose sensor" for insulin release. Activation of glucokinase increases the glucose sensitivity of insulin secretion, effectively lowering the glucose threshold for insulin secretion. Because of its potential to enhance insulin secretion and affect hepatic glucose metabolism, is being investigated for use as a treatment for hyperglycaemia, Globalagliatin( the active ingredient in SY-004 capsule) is being investigated for use as a treatment for T2DM patients. 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.
- Being tested
- Globalagliatin Hydrochloride, Placebo
- Keywords
- Type 2 Diabetes Mellitus, Glucokinase Activator
- Medical subject headings
- Hyperglycemia, Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Globalagliatin HydrochlorideDrug
Also called SY-004
once daily, oral
PlaceboDrug
once daily, oral
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
the mean change in glucose area under curve (AUC) from baseline.
Compared with placebo, the mean change in glucose AUC from baseline at D28.
Measured: 28 days
Secondary outcomes (5)
the fasting plasma glucose from baseline
Compared with placebo, the fasting plasma glucose from baseline at D7,D14,D21 and D28.
Measured: 7, 14, 21, 28 days
the changes of MMTT (mixed-meal tolerance test) results from baseline
Compared with placebo, the changes of MMTT (mixed-meal tolerance test) results from baseline at D28
Measured: 28 days
the mean changes of average 7-points blood glucose profiles from baseline
Compared with placebo, the mean changes of average 7-points blood glucose profiles from baseline at D7,D14,D21 and D28.
Measured: 7, 14, 21, 28 days
the mean changes of average 14-points blood glucose profiles from baseline
Compared with placebo, the mean changes of average 14-points blood glucose profiles from baseline at D7,D14,D21 and D28.
Measured: 7, 14, 21, 28 days
the mean changes of post-prandial blood glucose from baseline
Compared with placebo, the mean changes of post-prandial blood glucose from baseline at D7,D14,D21 and D28.
Measured: 7, 14, 21, 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jan 2018
- Study start3 Jan 2018
- Primary completion4 Jan 2019
- Study completion1 Dec 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hyperglycaemia (Diabetic)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yabao Pharmaceutical Group
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Lei Yang, Study director, Yabao pharmaceutical Group Co.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03414892
- Sponsor's protocol ID
- YB17071
- Status last verified
- Jan 2018
- First submitted
- 7 Jan 2018
- Last updated
- 3 Jan 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 33125674
Study at a glance
From the registry record, last updated by the sponsor on 3 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Placebo-controlled Study to Assess Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Globalagliatin Hydrochloride After Multiple Ascending Doses in Patients With Type 2 Diabetes Mellitus
- ClinicalTrials.gov ID
- NCT03414892
- Acronym / sponsor ID
- YB17071
- Keywords
- Type 2 Diabetes Mellitus, Glucokinase Activator
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Yabao Pharmaceutical GroupIndustry (pharma, biotech, devices)
- Study start
- 3 Jan 2018 (actual)
- Primary completion
- 4 Jan 2019 (actual)
- Study completion
- 1 Dec 2019 (actual)
- First posted
- 30 Jan 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
Glucokinase is a characteristic hexokinase isoenzyme in hepatocytes that catalyzes the first step in glucose metabolism. In addition to its role in glucose metabolism, glucokinase is expressed in pancreatic islet beta cells where it acts as a "glucose sensor" for insulin release. Activation of glucokinase increases the glucose sensitivity of insulin secretion, effectively lowering the glucose threshold for insulin secretion. Because of its potential to enhance insulin secretion and affect hepatic glucose metabolism, is being investigated for use as a treatment for hyperglycaemia, Globalagliatin( the active ingredient in SY-004 capsule) is being investigated for use as a treatment for T2DM patients. 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Globalagliatin Hydrochloride (SY-004) | Experimental | Drug: Globalagliatin HydrochlorideIf 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. |
| Placebo | Placebo comparator | Drug: PlaceboIf 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. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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.
- 18 kg/m2≤BMI≤35 kg/m2 at screening.
- 7% ≤ HbA1c ≤11% at screening.
Key exclusion criteria (30 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Globalagliatin HydrochlorideAlso: SY-004once daily, oral | Drug | Globalagliatin Hydrochloride (SY-004) |
| Placeboonce daily, oral | Drug | Placebo |
Primary outcome
the mean change in glucose area under curve (AUC) from baseline.
Time frame: 28 days
Compared with placebo, the mean change in glucose AUC from baseline at D28.
5 secondary outcomes
the fasting plasma glucose from baseline
Time frame: 7, 14, 21, 28 days
the changes of MMTT (mixed-meal tolerance test) results from baseline
Time frame: 28 days
the mean changes of average 7-points blood glucose profiles from baseline
Time frame: 7, 14, 21, 28 days
the mean changes of average 14-points blood glucose profiles from baseline
Time frame: 7, 14, 21, 28 days
the mean changes of post-prandial blood glucose from baseline
Time frame: 7, 14, 21, 28 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jan 2020.
- Derived from this study: PubMed 33125674Zheng 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lei Yang study director
Yabao pharmaceutical Group Co.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Globalagliatin Hydrochloride in people with Hyperglycaemia (Diabetic) and Type 2 Diabetes Mellitus, run by Yabao Pharmaceutical Group at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
the mean change in glucose area under curve (AUC) from baseline. (time frame: 28 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03414892, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jan 2020.