A Study to Access the Efficacy in Type 2 Diabetes Mellitus on Stable Metformin

NCT04662164 | Withdrawn Phase 1

• 1 other identifier: L47-DM-II-01
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a randomized, double-blind, placebo-controlled, repeat-dose study to evaluate the safety, tolerability, PK, and PD of L47 as an add-on treatment to stable metformin therapy in patients with T2DM. Approximately 30 subjects will be randomized into the study at up to two investigational sites. The study includes a screening period of up to 28 days, with a three-day, single-blind, placebo lead-in period; a four-week, double-blind treatment period; and a one-week follow-up period. There will be 2 inpatient stays (Day -3 to 2 and 27 to 29) and daily outpatient visits during treatment period. During the follow-up period, there will be 1 outpatient visit at the end of the study. There will be 3 cohorts of 10 subjects each to be enrolled sequentially. In each cohort, subjects will be randomized in a 4:1 ratio to receive either L47 or placebo subcutaneously. Subjects will monitor fasting capillary glucose (finger sticks or self-monitoring of blood glucose, SMBG) during the lead-in, treatment, and follow-up periods.

Conditions

Type 2 Diabetes Patients

Keywords

hepalatide; FBG; TG; TC; PK

Outcome Measures

Primary Outcomes (2)

• 24-hour weighed mean glucose (WMG)

  The change from baseline in the 24-hour WMG calculated is as the AUC0-24h divided by 24 using linear trapezoidal method. \[Time frame: Baseline (Day -1), to Day 28\]

  28 days

• AEs

  Number and percentage of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs), number of subjects discontinuing due to AEs

  28 days

Secondary Outcomes (1)

• fasting plasma glucose

  28 days

Study Arms (4)

placebo

PLACEBO COMPARATOR

control

Drug: hepalatide

4.2mg hepalatide

ACTIVE COMPARATOR

low dose

Drug: hepalatide

6.3mg hepalatide

ACTIVE COMPARATOR

middle dose

Drug: hepalatide

8.4mg hepalatide

ACTIVE COMPARATOR

high dose

Drug: hepalatide

Interventions

hepalatide DRUG

3 different dosage will be given sequentially to T2D patients

Also known as: L47

4.2mg hepalatide; 6.3mg hepalatide; 8.4mg hepalatide; 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:

• Subjects who have received a diagnosis of T2DM ≥3 months prior to screening
• Subjects who have taken a stable metformin dose for at least one month prior to screening and are not currently taking other anti-diabetic drugs
• Males or females between 18 and 70 years of age, inclusive. Females must have agreed to use appropriate birth control throughout the study or be surgically sterile (hysterectomy, tubal ligation, bilateral oophorectomy) or post-menopausal for 1 year (with follicle stimulating hormone in menopausal range). A serum pregnancy test was performed for women of childbearing potential at the screening visit and at Day -1.
• Male patients with sexual partners of childbearing potential and female patients of childbearing potential must have agreed to use 1 of the following contraception methods:
• One form of barrier method contraception (eg, latex condom with spermicide or a diaphragm with intravaginal spermicide or cervical cap with spermicide) in addition to a male patient's female partner(s) taking an oral contraceptive; or
• Two forms of barrier method contraception (eg, latex condom with spermicide AND a diaphragm with intravaginal spermicide or cervical cap with spermicide);
• Subjects who have a body mass index ≥19 kg/m2 and ≤35 kg/m2
• Subjects who have a Hemoglobin A1c(HBA1c) ≥6.5% and ≤10.5%, as assessed by the central laboratory
• Current non-smokers who have not used tobacco or nicotine in any form at least 6 months prior to dosing
• Currently have not used nicotine and non-nicotine vaping/electronic cigarette products in the last 6 months
• Fasting plasma glucose \>110 mg/dL and \<240 mg/dL;
• Willing and able to be confined to the investigational site as required by the protocol;
• Willing and able to comply with the investigational nature of the study and able to communicate well with the Principal Investigator and clinical staff; and
• Able to comprehend and willing to provide written informed consent in accordance with institutional and regulatory guidelines.

You may not qualify if:

• Have a condition that is a contraindication for use of metformin per Label at screening or at baseline visit;
• History of type 1 diabetes mellitus, or latent autoimmune diabetes in adults, diabetic neuropathy, retinopathy or nephropathy
• History of renal transplantation or are receiving renal dialysis at the time of screening
• History of severe symptomatic hypoglycemia within six months of screening
• History of diabetic ketoacidosis or other types of metabolic acidosis
• History of diabetic gastroparesis
• History of chronic or acute pancreatitis
• History of hemochromatosis
• History or presence of clinically significant cardiovascular disease (including a history of unstable angina, acute myocardial infarction, coronary artery bypass graft, percutaneous coronary intervention, or New York Heart Association Class III or IV congestive heart failure within six months prior to screening)
• Uncontrolled hypertriglycerides \>500 mg/dL
• History of acute or chronic renal disease; estimated glomerular filtration rate (eGFR) ≤60 ml/min/1.73m2
• Inability to tolerate subcutaneous injections
• History of allergy, sensitivity or intolerance to peptide products or history of severe hypersensitivity to drugs, foods or other environmental allergens
• History of coagulation disorders with a potential of causing excessive bleeding or a history of unexplained excessive bleeding
• Use of warfarin or other anti-coagulation drugs. The use of anti-platelet drugs such as acetylsalicylic acid (daily use) and/or clopidogrel that are prescribed for prevention of cardiovascular events is permitted.

Sponsors & Collaborators

• Shanghai HEP Pharmaceutical Co., Ltd.: lead

Study Design

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

Study Record Dates

• First Submitted: December 3, 2020
• First Posted: December 10, 2020
• Study Start: December 1, 2025
• Primary Completion: December 1, 2025
• Study Completion: December 1, 2025
• Last Updated: December 8, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share