Manidipine Versus Amlodipine in Patients With Hypertension

NCT03106597 | Terminated Phase 4

• 1 other identifier: KUGH15082 (MAAMA)
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of this study is to evaluate the effect of a third-generation Calcium Channel Blocker (CCB), manidipine, compared with second-generation Calcium Channel Blocker (CCB), amlodipine, on the development of peripheral edema using Direct Segmental Multi-Frequency Bioelectrical Impedance Analysis (DSM-BIA) method in patients with mild to moderate essential hypertension. Investigator expects this study could show more objective evidence of better safety of manidipine compared with amlodipine for peripheral edema.

Conditions

Hypertension

Keywords

Peripheral Edema; Bioimpedance Analysis

Outcome Measures

Primary Outcomes (1)

• Change in leg edema score (Extracellular Water(ECW) to Total Body Water(TBW))

  Up to 8 weeks

Secondary Outcomes (3)

• Changes in segmental (each arm/leg, trunk) edema score

  Up to 8 weeks

• Changes in Blood Pressure (BP)

  Up to 8 weeks

• Incidences of AEs

  Up to 8 weeks

Study Arms (2)

Manidipine 20mg

EXPERIMENTAL

50 patients will be administered orally manidipine 20mg/day after 1\~2 week run-in period

Drug: Manidipine 20mg

Amlodipine 10mg

ACTIVE COMPARATOR

50 patients will be administered orally amlodipine 10mg/day after 1\~2 week run-in period

Drug: Amlodipine 10mg

Interventions

Manidipine 20mg DRUG

After a 1\~2-week run-in period, patents will be randomized to receive manidipine (20 mg/day; n=50) for a 8-week open-labeled phase. Study drugs will be administered orally and once daily between 8:00am and 10:00am. BP, heart rate, adverse events and concomitant therapy are assessed and a physical examination is performed at each visit. A 12-lead standard ECG is obtained and hematology, clinical biochemistry and urine analysis investigations performed at the screening visit. A Bioelectrical Impedance Analysis (BIA) is undertaken at the screening visit and at the end of the 8-week treatment course. Patients have to attend the clinic visit every 4 weeks during the treatment period.

Also known as: Madipine Tab(Manidipine Hydrochloride) 20mg (CJ)

Manidipine 20mg

Amlodipine 10mg DRUG

After a 1\~2-week run-in period, patents will be randomized to receive amlodipine (10 mg/day; n=50) for a 8-week open-labeled phase. Study drugs will be administered orally and once daily between 8:00am and 10:00am. BP, heart rate, adverse events and concomitant therapy are assessed and a physical examination is performed at each visit. A 12-lead standard ECG is obtained and hematology, clinical biochemistry and urine analysis investigations performed at the screening visit. A Bioelectrical Impedance Analysis (BIA) is undertaken at the screening visit and at the end of the 8-week treatment course. Patients have to attend the clinic visit every 4 weeks during the treatment period.

Also known as: Amlodipine Pfizer 10mg (Pfizer)

Amlodipine 10mg

Eligibility Criteria

• Age: 20 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female outpatients between the ages of 20 and 80 years with uncomplicated essential hypertension are eligible.
• The patients are newly diagnosed or known hypertensive subjects who were not taking antihypertensive agents for more than the last 4 weeks.

You may not qualify if:

• Patients are excluded from the study if they have any evidence of clinically significant concurrent medical conditions including cardiac, renal, hepatic, gastrointestinal, or endocrinologic disease.
• Patients are also excluded if they have known hypersensitivity or serious drug reactions to Calcium Channel Blockers (CCBs), any evidence of prior deep vein thrombosis, lymphatic disease, or concurrent requirement for medications that could affect Blood Pressure (BP) or salt and water retention (e.g, nonsteroidal antinflammatory drugs, estrogen containing drugs).

Sponsors & Collaborators

• Korea University Guro Hospital: lead
• Takeda Pharmaceuticals International, Inc.: collaborator

Study Sites (3)

Yonsei University Severance Hospital

Seoul, 03722, South Korea

Location

Korea University Guro Hospital

Seoul, 08308, South Korea

Location

Yonsei University Wonju Hospital

Wŏnju, 26426, South Korea

Location

Related Publications (10)

• Richy FF, Laurent S. Efficacy and safety profiles of manidipine compared with amlodipine: a meta-analysis of head-to-head trials. Blood Press. 2011 Feb;20(1):54-9. doi: 10.3109/08037051.2010.518670. Epub 2010 Oct 14.

  PMID: 20945994 BACKGROUND

• Opie LH. Calcium channel antagonists. Part IV: Side effects and contraindications drug interactions and combinations. Cardiovasc Drugs Ther. 1988 Jul;2(2):177-89. doi: 10.1007/BF00051233.

  PMID: 3154704 BACKGROUND

• Makani H, Bangalore S, Romero J, Wever-Pinzon O, Messerli FH. Effect of renin-angiotensin system blockade on calcium channel blocker-associated peripheral edema. Am J Med. 2011 Feb;124(2):128-35. doi: 10.1016/j.amjmed.2010.08.007.

  PMID: 21295192 BACKGROUND

• Messerli FH, Oparil S, Feng Z. Comparison of efficacy and side effects of combination therapy of angiotensin-converting enzyme inhibitor (benazepril) with calcium antagonist (either nifedipine or amlodipine) versus high-dose calcium antagonist monotherapy for systemic hypertension. Am J Cardiol. 2000 Dec 1;86(11):1182-7. doi: 10.1016/s0002-9149(00)01199-1.

  PMID: 11090788 BACKGROUND

• Fogari R. Ankle oedema and sympathetic activation. Drugs. 2005;65 Suppl 2:21-7. doi: 10.2165/00003495-200565002-00004.

  PMID: 16398059 BACKGROUND

• Weir MR, Rosenberger C, Fink JC. Pilot study to evaluate a water displacement technique to compare effects of diuretics and ACE inhibitors to alleviate lower extremity edema due to dihydropyridine calcium antagonists. Am J Hypertens. 2001 Sep;14(9 Pt 1):963-8. doi: 10.1016/s0895-7061(01)02167-7.

  PMID: 11587165 BACKGROUND

• Fogari R, Malamani G, Zoppi A, Mugellini A, Rinaldi A, Fogari E, Perrone T. Effect on the development of ankle edema of adding delapril to manidipine in patients with mild to moderate essential hypertension: a three-way crossover study. Clin Ther. 2007 Mar;29(3):413-8. doi: 10.1016/s0149-2918(07)80079-8.

  PMID: 17577462 BACKGROUND

• Seo HS, Kim EJ, Kim SW, Im SI, Na JO, Choi CU, Lim HE, Won Kim J, Rha SW, Park CG. Extracellular fluid adjusted for body size is contracted in hypertension. Hypertens Res. 2013 Oct;36(10):916-21. doi: 10.1038/hr.2013.68. Epub 2013 Jul 11.

  PMID: 23842617 BACKGROUND

• Ling CH, de Craen AJ, Slagboom PE, Gunn DA, Stokkel MP, Westendorp RG, Maier AB. Accuracy of direct segmental multi-frequency bioimpedance analysis in the assessment of total body and segmental body composition in middle-aged adult population. Clin Nutr. 2011 Oct;30(5):610-5. doi: 10.1016/j.clnu.2011.04.001. Epub 2011 May 8.

  PMID: 21555168 BACKGROUND

• Schoeller DA, Alon A, Manekas D, Mixson LA, Lasseter KC, Noonan GP, Bolognese JA, Heymsfield SB, Beals CR, Nunes I. Segmental bioimpedance for measuring amlodipine-induced pedal edema: a placebo-controlled study. Clin Ther. 2012 Mar;34(3):580-92. doi: 10.1016/j.clinthera.2012.01.018. Epub 2012 Mar 3.

  PMID: 22385927 BACKGROUND

MeSH Terms

Conditions

Hypertension

Interventions

manidipine; Amlodipine

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Dihydropyridines; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Eung Ju Kim, MD

  Professor

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Blinded-endpoint
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: 1. Manidipine 20mg/day, Amlodipine 10mg/day 2. Sealed envelope method randomization according to gender and age * 25 males under 55 years old * 25 males more than 55 years old * 25 females under 55 years old * 25 females more than 55 years old

Study Record Dates

• First Submitted: March 29, 2017
• First Posted: April 10, 2017
• Study Start: August 20, 2015
• Primary Completion: May 15, 2018
• Study Completion: August 14, 2019
• Last Updated: September 4, 2020

Record last verified: 2017-04

Data Sharing

• IPD Sharing: Will not share

Locations

KR (3)