A TSHRN1201 Sub-study-To Evaluate the Effects of add-on Ranolazine on Exercise Tolerance and Angina Frequency

A TSHRN1201 Sub-study-To Evaluate the Effects of add-on Ranolazine on Exercise Tolerance and Angina Frequency in Patients With Stable Angina Pectoris.

This is a double-blind, randomized, placebo-controlled, and parallel study. The study is comprised of three main phases: a single-blind placebo run-in qualifying phase lasting about 14 days, a double-blind treatment phase of 12 weeks, and a 2-week follow-up phase. Approximately 18 patients will be enrolled and randomly assigned to receive placebo or 1,000 mg of extended-release Ranolazine twice-daily for 12 weeks to reach 14 evaluable patients at the end of the study.

Study Overview

• Status: Completed
• Conditions: Angina
• Intervention / Treatment: Drug: Ranolazine; Drug: Placebos

Detailed Description

This is a double-blind, randomized, placebo-controlled, and parallel study. The study is comprised of three main phases: a single-blind placebo run-in qualifying phase lasting about 14 days, a double-blind treatment phase of 12 weeks, and a 2-week follow-up phase. Approximately 18 patients will be enrolled and randomly assigned to receive placebo or 1,000 mg of extended-release Ranolazine twice-daily for 12 weeks to reach 14 evaluable patients at the end of the study.

Patients with chronic angina pectoris will be screened for eligibility after providing informed consent. Patients present with the symptoms of stable angina after withdrawn from other antianginal agents and given the required background therapy for at least 5 days will be qualified for entering this study and performing 1st ETT qualifying test.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Taiwan
  • Zhongzheng Dist
    • Taipei, Zhongzheng Dist, Taiwan, 10048
      • National Taiwan University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female patients aged ≥ 20 years old.
2. A minimum 3-month history of stable angina.

3. Patients with diagnosis of coronary artery disease (CAD) via at least one of the following criteria:

   • Angiographic evidence of ≥ 50% stenosis of ≥ 1 major coronary artery;
   • CT angiographic evidence of ≥ 50% stenosis of ≥ 1 major coronary artery;

   • History of previous myocardial infarction (MI)*;

     *Previous MI history of patients has to be occurred and diagnosed at least 2 months prior entering this study.

   • A stress-induced reversible perfusion defect identified by radionuclide or echocardiographic imaging.
4. Patients present with the symptoms of stable angina after withdrawn from other antianginal drugs and given the required background therapy for at least 5 days will be qualified for entering this study and performing 1st ETT qualifying test.
5. Patients developed exercise-induced ECG ischemia during two qualifying exercise treadmill tests. The difference between twotests should be ≤ 20% of the longer test or ≤ 1 minute.
6. Willing and able to provide a written informed consent.

Exclusion Criteria:

1. Factors that might compromise ECG or ETT interpretation.

   • Patients with resting ST-segment depression ≥ 1mm in any lead.
   • Left bundle-branch block.
   • Patients implanted with pacemaker.
   • Patients under Digitalis therapy.
2. Patients with family history of (or congenital) long QT syndrome.
3. Patients with congenital heart disease.
4. Patients with uncorrected valvular heart disease.
5. Patients with unstable angina, or MI, or coronary revascularization procedure ≤ 2 months prior enter this study.

6. Female who is pregnant/lactating or planning to be pregnant, or female of childbearing potential* who is not using medically recognized method of contraception.

   *Other than those who have been surgically sterilized (defined as having undergone hysterectomy or bilateral oophorectomy or bilateral salpingectomy; tubal ligation alone is not considered sufficient) or one year post-menopausal.

7. Patients are under any one of the following conditions:

   • New York Heart Association (NYHA) Class III or Class IV congestive heart failure (CHF);
   • QTc > 450 msec at screening;
   • Active myocarditis, pericarditis, hypertrophic cardiomyopathy;
   • Uncontrolled hypertension (defined as SBP > 180 mmHg). Voltage criteria for left ventricular hypertrophy in the absence of repolarization abnormalities will not be exclusion criteria.
8. Use of any investigational product ≤ 4 weeks prior to screening.
9. Patients with severe hepatic disease (e.g., liver cirrhosis).
10. Patients with impaired renal function (defined as serum Cr >1.5 mg/dl).
11. Patients with any condition or disease which is considered not suitable for this study by investigator.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment groups; Ranolazine 1000 mg	Drug: Ranolazine; Oral, b.i.d; Other Names: RNTA
Placebo Comparator: Control group; Placebos	Drug: Placebos; Oral, b.i.d; Other Names: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ETT performing duration	To compare the change from baseline of ETT performing duration between add-on Ranolazine and placebo	at trough (12 hours after dosing) at Week 12

Collaborators and Investigators

• Sponsor: TSH Biopharm Corporation Limited

Study record dates

Study Major Dates

• Study Start (Actual): June 7, 2018
• Primary Completion (Actual): March 30, 2019
• Study Completion (Actual): March 31, 2019

Study Registration Dates

• First Submitted: January 7, 2018
• First Submitted That Met QC Criteria: January 16, 2018
• First Posted (Actual): January 17, 2018

Study Record Updates

• Last Update Posted (Actual): April 10, 2019
• Last Update Submitted That Met QC Criteria: April 8, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Pain; Neurologic Manifestations; Chest Pain; Angina Pectoris; Molecular Mechanisms of Pharmacological Action; Membrane Transport Modulators; Sodium Channel Blockers; Ranolazine
• Other Study ID Numbers: TSHRN1701

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No