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

T2DM Clinical Trial

Official title:

A Multicenter, Randomized, Double-Blind, Parallel, Active-Controlled Phase III Study on Metformin Combined With THR-1442 or Dapagliflozin in T2DM

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05159882
• Other study ID #: THR-1442-C-606
• Status: Recruiting
• Phase: Phase 3
• Start date: April 15, 2021
• Est. completion date: September 30, 2022

Study information

• Verified date: November 2021
• Source: Newsoara Biopharma Co., Ltd.
• Contact: Owen Zhang
• Phone: 8621-52998027
• Email: owen.zhang[@]newsoara.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 390
• Est. completion date: September 30, 2022
• Est. primary completion date: September 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• T2DM

Intervention

Drug:
• THR-1442 and Dapagliflozin placebo
THR-1442 tablets 20mg and Dapagliflozin tablets placebo
• Dapagliflozin 10mg and THR1442 placebo
Dapagliflozin tablets 10mg and THR-1442 tablets placebo

Locations

Country	Name	City	State
China	China-Japan Friendship Hospital	Beijing
China	The First People's Hospital of Changzhou	Changzhou	Jiangsu
China	The Fourth Hospital of Harbin Medical University	Harbin	Heilongjiang
China	Affiliated Huzhou Hospital Zhejiang University School of Medical	Huzhou	Zhejiang
China	Shandong Province Qianfoshan Hospital	Jinan	Shandong
China	The Second Affiliated Hospital of Nanjing Medical University	Nanjing	Jiangsu

Sponsors (1)

Lead Sponsor	Collaborator
Newsoara Biopharma Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in HbA1c at Week 24	HbA1c was obtained at baseline and at Week 24	Baseline to week 24
Secondary	Change From Baseline in FPG at Week 24	FPG was obtained at baseline and at Week 24	Baseline, up to 24 weeks
Secondary	Change in Body Weight From Baseline to Week 24	Body Weight was obtained at baseline and at week 24	Baseline, up to 24 weeks
Secondary	Changes in blood pressure from baseline to week 24	Blood pressure was obtained at baseline and at week 24	Baseline, up to 24 weeks