Comparing Safety and Efficacy of Amlodipine Verses S Amlodipine in Patients With Essential Hypertension

A 12 Weeks, Multi-center, Randomized, Open Label, Active Control, Phase IV Clinical Trial to Compare Evaluated Improvement of Edema Index, Safety and Efficacy of Amlodipine Versus S Amlodipine in Patients With Essential Hypertension

As a third-generation dihydropyridine calcium channel blocker (CCB), Amlodipine is mainly used in a single therapy or combined therapy for hypertension or angina.

Edema, one of the most common side effects of dihydropyridine CCB formulations, may lead to drug control or discontinuation of drugs.

This clinical study intends to assess the safety and efficacy of S-amlodipine, which is assessed to be superior to Amlodipine in the aspects of antihypertensive effect and side effects, in edema of patients with essential hypertension.

1. Clinical Study Design

   - In this clinical study, Part 1 is conducted as a preliminary study on 10 subjects at a single center, and based on the results of Part 1, the sponsor and the principal investigator determine whether to proceed with Part 2. With Part 2 as the multicenter main study conducted on the remaining 70 subjects, 80 subjects in total have been planned for Part 1 and Part 2.

2. Interim analysis

   - The interim analysis is conducted when the study on 10 subjects at a Part 1 single center has been completed; the analysis is made on all endpoints planned for this clinical study.

3. Clinical study methods - During screening, subjects who have voluntarily signed the Informed Consent Form are tested for eligibility to this clinical study.

After a wash-out period of at least two weeks, subjects who satisfy the inclusion/exclusion criteria are randomly assigned to two groups (S-amlodipine group, Amlodipine group). Thereafter, the subjects are enrolled and orally administered with the investigational product once a day for 12 weeks, during which they receive a total of five visits for tests conducted for assessment of efficacy and safety.

(In case of confirmed eligibility without administration of contraindications, the wash-out period may be omitted and Visits 1 and 2 may be paid on the same day)

Inclusion Criteria:

1. Patients with essential hypertension and diagnosed with stage 1-2 hypertension in accordance with the 2019 Korean Society of Hypertension criteria (SBP ≥ 140 mmHg or DBP ≥ 90 mmHg)

2. Where a subject and his/her spouse (partner) have agreed to use medically acceptable contraceptives in the following during participation in this clinical study:

   • Use of intrauterine device with proven failure rate of pregnancy;
   • Simultaneous use of blocking contraception and spermicide;
   • Has had a vasectomy;
   • Has had a salpingectomy, tubal ligation, or hysterectomy;

3. Those who have made voluntary decisions to participate in this clinical study and have consented to the Informed Consent Form in writing;

4. Those who are able to understand and follow instructions and participate throughout the entire clinical study

Exclusion Criteria:

1. Patients with uncontrolled, high-risk hypertension (SBP≥180mm Hg and DBP≥110mm Hg);

2. Those who have a history of secondary hypertension and any history of suspected secondary hypertension (aortic congestion, hyperaldosteronism, renal artery stenosis, Cushing's disease, chromaffinoma, polycystic renal disease, etc.);

3. Those who fall under one or more of the following items that may cause edema without underlying diseases:

   • Those who have been diagnosed with myocardial infarction or heart failure within 6 months of screening;
   • Those who have been diagnosed with a cerebrovascular accident (CVA) within 6 months of screening;
   • Patients with renal failure requiring dialysis or those with edema caused by renal dysfunction (renal salt retention);
   • Those who have uncontrolled diabetes (HbA1c> 10.0%) or diabetic edema;
   • Patients with severe liver dysfunction or edema caused by liver disease (cirrhosis);
   • Other patients with hypothyroidism, proteinuria, and problems at the joint or ankle joint

4. Those who have cerebrovascular disease, unstable angina, or transient ischemic attack, or those who have had coronary artery bypass graft or coronary angioplasty;

5. Patients who may develop edema by concomitant drugs at screening:

   • Drugs that constrict intrarenal blood vessels (e.g. nonsteroidal anti-inflammatory drugs, cyclosporine, etc.);
   • Drugs that dilate arterioles (e.g. vasodilators, etc.);
   • Drugs that increase sodium reabsorption in the kidneys (e.g. steroids, etc.);
   • Drugs that damage capillaries (e.g. interleukin-2, etc.);
   • Glitazone-based drugs for diabetes

6. Those who show hypersensitive reaction* to the investigational product;

7. Those who are taking the following drugs that may cause drug interactions:

   • Drugs that may change the plasma concentration of amlodipine [e.g. CYP3A4 inducers (e.g. rifampicin, St. John's wort (Hypericum perforatum), etc.);
   • Drugs that may increase the antihypertensive action [e.g. other antihypertensives (calcium channel blockers, beta blockers, ACEi, ARB, alpha blockers, diuretics, nitroglycerin), tricyclic antidepressants (amitriptyline, desipramine, imipramine, nortriptyline, protriptyline, trimipramine, etc.), nitrate formulation, baclofen, pioglitazone, sildenafil, etc.];
   • Systemic corticosteroids (fluocinolone, triamcinolone), etc.: Local application allowed;
   • Drugs that may increase the inhibitory action of muscle contraction [e.g. antiarrhythmics (amiodarone, quinidine, etc.);
   • Drugs that may cause ventricular spasms (e.g. intravenous administration of dantrolene and verapamil);
   • Drugs that may increase the risk of hypotension [e.g. CYP3A4 inhibitors (clarithromycin), etc.]

8. Patients in a state of chronic inflammation requiring chronic anti-inflammatory treatment;

9. Those who have participated in other interventional clinical studies within 6 months of screening;

10. Those who have been diagnosed as having malignant tumors within 5 years of screening;

11. Those who showed clinically significant abnormal results in electrocardiogram and laboratory tests at screening;

12. Those who are pregnant or lactating, or have been confirmed as being pregnant through the Urine HCG test;

13. Those who have been judged to be inappropriate to participate in the clinical study by the principal investigator or subinvestigator.