Safety and Efficacy of THR-1442 Compared to Dapagliflozin as Add-on Therapy to Metformin in T2DM

Phase 3

• Conditions: T2DM
• Interventions: Drug: THR-1442 and Dapagliflozin placebo; Drug: Dapagliflozin 10mg and THR1442 placebo

• Registration Number: NCT05159882
• Lead Sponsor: Newsoara Biopharma Co., Ltd.

Brief Summary

The purpose of this study is to investigate the effect of THR-1442 compared to Dapagliflozin as an add-on therapy to metformin in lowering hemoglobin A1c (HbA1c) levels in subjects with type 2 diabetes mellitus (T2DM).

Detailed Description

Approximately 390 subjects with inadequately controlled T2DM on metformin were to be recruited from China. Subjects were randomly assigned to receive THR-1442 tablet, 20 mg, or Dapagliflozin tavlet,10 mg, in a ratio of 1:1 once daily for 24 weeks. Subjects were to continue taking metformin for the duration of the study.

Study Timeline

• Study Start: 2021-04-15
• Status Verified: 2021-11
• Study First Submitted: 2021-12-03
• Study First Submitted QC: 2021-12-03
• Last Update Submitted: 2021-12-03
• Study First Posted: 2021-12-16
• Last Update Posted: 2021-12-16
• Primary Completion: 2022-09-30
• Study Completion: 2022-09-30

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 390

Inclusion Criteria

1. Male or female adult subjects ≥ 18 years of age
2. If subjects are female of childbearing potential, subjects must be negative on the pregnancy test and abstain from coitus or use effective contraceptive measures during the entire study until 30 days after the investigational product is discontinued
3. Subjects diagnosed with T2DM, with a HbA1c level of 7.5-11% (inclusive) at screening and 7.0-10.5% (inclusive) at enrollment
4. Subjects who are treated with a stable dose of ≥ 1500 mg/day metformin monotherapy along with diet and exercise counseling for at least 8 weeks prior to screening
5. Subjects with a BMI of 19-35kg/m2 (inclusive) at screening
6. If applicable, taking stable doses of treatment for dyslipidemia and/or hypertension for 30 days prior to screening. Subjects who do not need to be treated with dyslipidemia or hypertension by the investigator's judgment are also eligible for the study

Exclusion Criteria

1. History of diabetes insipidus
2. Definitive diagnosis of Type 1 diabetes mellitus, maturity-onset diabetes of the young (MODY), or secondary diabetes mellitus
3. Symptoms of diabetes mellitus inadequate control, resulting in the inability to participate in this trial, including but not limited to significant polyuria and polydipsia within 3 months prior to the screening visit and weight loss > 10%
4. History of urinary tract or genital infection within 6 months prior to screening, or ≥ 3 times of urinary tract or genital infections within 6 months prior to screening that require treatments
5. Two or more consecutive SMBG measures ≥ 250 mg/dL (13.9 mmol/L) prior to randomization (run-in period) accompanied by clinical signs or symptoms of hyperglycemia prior to randomization, including weight loss, blurred vision, increased thirst, increased urination, or fatigue
6. History of diabetic ketoacidosis or hyperosmolar non-ketonic coma within 6 months prior to screening
7. History of severe fracture secondary to osteoporosis
8. Poorly controlled hypertension: blood pressure systolic ≥ 160 mmHg and/or blood pressure diastolic ≥ 100 mmHg
9. Surgical history resulting in unstable weight or scheduled for such surgery during the study period
10. Any unstable endocrine, psychiatric, or rheumatoid disease as assessed by the investigator
11. Possible risk of dehydration or body fluid exhaustion based on the investigator's judgment that may affect the interpretation of efficacy or safety data
12. Currently having or had a history of alcohol or drug abuse within the past 6 months
13. Presence of the following cardiovascular/vascular disorders within 6 months prior to screening:
14. Unstable or rapidly progressive renal disorder
15. Congenital renal glycosuria
16. Major liver disease, including but not limited to hepatitis chronic active and/or significant hepatic function abnormal, including ALT and/or AST ≥ 3 × upper limit of normal (ULN) and/or total bilirubin ≥ 2 × ULN; or medical history of severe hepatobiliary disease; or history of any drug-related hepatotoxicity;
17. Current positive serological test result for infectious hepatitis, including known positivity to hepatitis B surface antigen and hepatitis C antibody

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
THR-1442 20mg	THR-1442 and Dapagliflozin placebo	Each subject will receive THR-1442 20 mg and Dapagliflozin placebo, once daily for the duration of the study.
Dapagliflozin10mg	Dapagliflozin 10mg and THR1442 placebo	Each subject will receive Dapagliflozin 10 mg and THR-1442 placebo, once daily for the duration of the study.

Primary Outcome Measures

Name	Time	Method
Change From Baseline in HbA1c at Week 24	Baseline to week 24	HbA1c was obtained at baseline and at Week 24

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in FPG at Week 24	Baseline, up to 24 weeks	FPG was obtained at baseline and at Week 24
Change in Body Weight From Baseline to Week 24	Baseline, up to 24 weeks	Body Weight was obtained at baseline and at week 24
Changes in blood pressure from baseline to week 24	Baseline, up to 24 weeks	Blood pressure was obtained at baseline and at week 24

Trial Locations

Locations (6)

The Fourth Hospital of Harbin Medical University; 🇨🇳 Harbin, Heilongjiang, China

The First People's Hospital of Changzhou; 🇨🇳 Changzhou, Jiangsu, China

The Second Affiliated Hospital of Nanjing Medical University; 🇨🇳 Nanjing, Jiangsu, China

Affiliated Huzhou Hospital Zhejiang University School of Medical; 🇨🇳 Huzhou, Zhejiang, China

Shandong Province Qianfoshan Hospital; 🇨🇳 Jinan, Shandong, China

China-Japan Friendship Hospital; 🇨🇳 Beijing, China