QR12000 Compound Tablets in Patients with Moderate to Severe Essential Hypertension

A Multicenter, Randomized, Double-blind, and Active-controlled Parallel Study to Evaluate the Efficacy and Safety of QR12000 Compound Tablets and Sacubitril/valsartan Tablets in Patients with Moderate to Severe Essential Hypertension

The purpose of the study is to evaluate the efficacy and safety of QR12000 75mg, QR12000 150mg and Sacubitril/valsartan 200mg in patients with moderate to severe essential hypertension.

Study Overview

• Status: Not yet recruiting
• Conditions: Essential Hypertension
• Intervention / Treatment: Drug: QR12000 75mg; Drug: QR12000 150mg placebo; Drug: Sacubitril/valsartan 200mg placebo; Drug: QR12000 75mg placebo; Drug: QR12000 150mg; Drug: Sacubitril/valsartan 200mg

• Study Type: Interventional
• Enrollment (Estimated): 810
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Wuhan Createrna Science and Technology Co.,Ltd; Phone Number: +86 027-68788900; Email: lcyxzx@createrna.com

Study Locations

• China
  • Beijing
    • Peking, Beijing, China, 100034
      • Peking University First Hospital
      • Contact: Jianping Li; Phone Number: +86 010-83572211; Email: lijianping03455@pkufh.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Subjects who can understand and are willing to complying with protocol requirement and sign the informed consent form.
2. Man or woman aged 18 years to 75 years (inclusive), with BMI≤30 kg/m2.
3. Patients with moderate to severe hypertension. Untreated patients must have an msSBP ≥ 160 mmHg and < 190 mmHg at the screening and randomization visit; Treated patients must have an msSBP≥150 mmHg and <180 mmHg or msSBP≥140 mmHg and <170 mmHg at the screening visit based on numbers of antihypertensive and msSBP≥160 mmHg <190 mmHg at the randomization visit; Patients must have an absolute difference of ≤20 mmHg in msSBP between randomization visit and the immediately preceding visit.
4. Subjects who agree to use adequate contraception from 2 weeks prior to screening to 1 month after last dose.

Exclusion Criteria:

1. History or evidence of a secondary form of hypertension.
2. History of peripheral arterial occlusive disease and Raynaud's syndrome.
3. History of hyperthyroidism.
4. History of hypotension.
5. History of angioedema, drug-related or otherwise.
6. Suffered by severe cerebrovascular disease within 1 year prior to screening.
7. Suffered by severe heart disease within 1 year prior to screening
8. History of severe or malignant retinopathy.
9. History of aortic aneurysm or dissection, cardiac surgery, or percutaneous coronary intervention within 1 year prior to screening.
10. History of malignant tumor within 5 years prior to screening.
11. Poorly controlled diabetes prior to screening
12. History of severe autoimmune diseases.
13. History of severe mental disorder.
14. Clinically significant laboratory abnormalities.
15. History of allergy to the test drug, active control drug, or drugs similar to the test drug and positive control drug or related excipients.
16. Undergone gastrointestinal surgery that could significantly alter drug absorption, distribution, metabolism, and excretion, or with severe gastrointestinal diseases, dysphagia, or recurrent vomiting that causes difficulty in eating or taking medication.
17. Intolerance to the run-in period.
18. Poor medication compliance or other non-compliance during run-in period.
19. Participated in any interventional clinical trial within 3 months prior to screening, plan to participate in another clinical trial during the period of this trial, or plan to participate in another clinical trial within 1 month after the end of this trial.
20. History of alcohol abuse within 6 months prior to screening or evidence of drug abuse.
21. Not agree or unable to comply with the restrictions on concomitant treatment during the study.
22. Pregnancy test positive, lactating women, or women planning to become pregnant.
23. High-altitude workers or large motor vehicle drivers and other professionals engaged in hazardous mechanical operations.
24. Other conditions that by the investigator's discretion may interfere with efficacy or safety assessment of the study, or pose a great risk to the subject.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: QR12000 75mg; Participants will be treated with one tablet of QR12000 75mg, one tablet of QR12000 150mg placebo and one tablet of Sacubitril/valsartan 200 mg placebo once daily for up to 8 weeks. Participants continue with one tablet of QR12000 150mg once daily for 44 weeks during TOP observation period.	Drug: QR12000 75mg; QR12000 75mg QD; Drug: QR12000 150mg placebo; Matching placebo of QR12000 150mg QD; Drug: Sacubitril/valsartan 200mg placebo; Matching placebo of Sacubitril/valsartan 200mg QD
Experimental: QR12000 150mg; Participants will be treated with one tablet of QR12000 150mg, one tablet of QR12000 75mg placebo and one tablet of Sacubitril/valsartan 200 mg placebo once daily for up to 8 weeks. Participants continue with one tablet of QR12000 150mg once daily for 44 weeks during TOP observation period.	Drug: Sacubitril/valsartan 200mg placebo; Matching placebo of Sacubitril/valsartan 200mg QD; Drug: QR12000 75mg placebo; Matching placebo of QR12000 75mg QD; Drug: QR12000 150mg; QR12000 150mg QD
Active Comparator: Sacubitril/valsartan 200 mg; Participants will be treated with one tablet of Sacubitril/valsartan 200 mg, one tablet of QR12000 75mg placebo and one tablet of QR12000 150mg placebo once daily for up to 8 weeks. Participants continue with one tablet of QR12000 150mg once daily for 44 weeks during TOP observation period.	Drug: QR12000 150mg placebo; Matching placebo of QR12000 150mg QD; Drug: QR12000 75mg placebo; Matching placebo of QR12000 75mg QD; Drug: Sacubitril/valsartan 200mg; Sacubitril/valsartan 200mg QD

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP)	The change in msSBP measured at Week 8 relative to baseline.	Baseline and week 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Mean Sitting Diastolic BP (msDBP)	The change in msDBP measured at Week 8 relative to baseline.	Baseline and week 8
Change From Baseline in Mean Ambulatory Systolic/Diastolic BP (maSBP/maDBP)	The change in maSBP/maDBP measured at Week 8 relative to baseline.	Baseline and week 8
Change From Baseline in Daytime ( > 6am and ≤ 10 pm) or Nighttime (> 10 pm and ≤ 6 am) maSBP/maDBP	The change in Daytime or Nighttime maSBP/maDBP measured at Week 8 relative to baseline.	Baseline and week 8
Percentage of Participants Achieving BP Control	BP control is defined as msSBP <140 mm Hg and msDBP <90 mm Hg.	Baseline and week 8
Percentage of Participants Achieving BP Response	BP Response is defined as msSBP <140 mm Hg and/or a reduction of ≥20 mm Hg from Baseline and msDBP <90 mm Hg and/or a reduction of ≥10 mm Hg from Baseline.	Baseline and week 8
Change From Baseline in msSBP/msDBP	The change in msSBP/msDBP measured at Week 28 and Week 52 relative to baseline.	Baseline, week 28 and week 52

Collaborators and Investigators

• Sponsor: Wuhan Createrna Science and Technology Co., Ltd

Study record dates

Study Major Dates

• Study Start (Estimated): December 30, 2024
• Primary Completion (Estimated): April 30, 2026
• Study Completion (Estimated): February 28, 2027

Study Registration Dates

• First Submitted: November 29, 2024
• First Submitted That Met QC Criteria: November 29, 2024
• First Posted (Actual): December 4, 2024

Study Record Updates

• Last Update Posted (Estimated): December 6, 2024
• Last Update Submitted That Met QC Criteria: December 3, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Essential Hypertension; Hypertension; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Valsartan; Sacubitril and valsartan sodium hydrate drug combination
• Other Study ID Numbers: QR12000-GXY-3-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No