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

• ClinicalTrials.gov Identifier: NCT05159882
• Recruitment Status: Unknown
• First Posted: December 16, 2021
• Last Update Posted: December 16, 2021
• Sponsor: Newsoara Biopharma Co., Ltd.
• Information provided by (Responsible Party): Newsoara Biopharma Co., Ltd.

Tracking Information

• First Submitted Date: December 3, 2021
• First Posted Date: December 16, 2021
• Last Update Posted Date: December 16, 2021
• Actual Study Start Date: April 15, 2021
• Estimated Primary Completion Date: September 30, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 3, 2021)

Change From Baseline in HbA1c at Week 24 [ Time Frame: Baseline to week 24 ]

HbA1c was obtained at baseline and at Week 24

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: December 3, 2021)

• Change From Baseline in FPG at Week 24 [ Time Frame: Baseline, up to 24 weeks ]
  FPG was obtained at baseline and at Week 24
• Change in Body Weight From Baseline to Week 24 [ Time Frame: Baseline, up to 24 weeks ]
  Body Weight was obtained at baseline and at week 24
• Changes in blood pressure from baseline to week 24 [ Time Frame: Baseline, up to 24 weeks ]
  Blood pressure was obtained at baseline and at week 24

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Safety and Efficacy of THR-1442 Compared to Dapagliflozin as Add-on Therapy to Metformin in T2DM
• Official Title: A Multicenter, Randomized, Double-Blind, Parallel, Active-Controlled Phase III Study on Metformin Combined With THR-1442 or Dapagliflozin in T2DM
• 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 Type: Interventional
• Study Phase: Phase 3

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

THR-1442 tablets, 20 mg; Double-Blind; Each subject will receive THR-1442, 20 mg once daily for the duration of the study.

Masking: Triple (Participant, Care Provider, Investigator)
Masking Description:

Dapagliflozin tablets, 10mg; Double Blind; Each subject will receive Dapagliflozin (active tablet) once daily for the duration of the study.

Primary Purpose: Treatment

• Condition: T2DM

Intervention

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

Study Arms

• Experimental: THR-1442 20mg
  Each subject will receive THR-1442 20 mg and Dapagliflozin placebo, once daily for the duration of the study.
  Intervention: Drug: THR-1442 and Dapagliflozin placebo
• Active Comparator: Dapagliflozin10mg
  Each subject will receive Dapagliflozin 10 mg and THR-1442 placebo, once daily for the duration of the study.
  Intervention: Drug: Dapagliflozin 10mg and THR1442 placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: December 3, 2021): 390
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: September 30, 2022
• Estimated Primary Completion Date: September 30, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China

Administrative Information

• NCT Number: NCT05159882
• Other Study ID Numbers: THR-1442-C-606
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Newsoara Biopharma Co., Ltd.
• Original Responsible Party: Same as current
• Current Study Sponsor: Newsoara Biopharma Co., Ltd.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Newsoara Biopharma Co., Ltd.
• Verification Date: November 2021