Pharmacokinetic Properties of Isosorbide-5-mononitrate Under Fasting and Fed Condition in Healthy Male Subjects

NCT02101710 | Completed Phase 1 DMC

• 1 other identifier: HD0001
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

This study it to evaluate the bioequivalence of Elantan SR 60 mg compared to Imdur SR 60 mg in sixty healthy Korean male subjects.

Conditions

Healthy

Keywords

Bioequivalence; Isosorbide 5-mononitrate; Elantan; Imdur; Korean; Healthy

Outcome Measures

Primary Outcomes (2)

• Area Under the Concentration-time Curve vs. time curve observed from time Baseline to the Last Quantifiable point (AUC(0-t))

  Samples will be taken predose and 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24 and 36 hr post-dose

• Maximum Observed Plasma Concentration (Cmax)

  Samples will be taken predose and 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24 and 36 hr post-dose

Secondary Outcomes (8)

• Area under the plasma concentration-time curve from zero up to infinity (AUC(0-inf))

  Samples will be taken 0 (predose) and 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24 and 36 hr post-dose

• Time to reach a maximum plasma concentration (tmax)

  Samples will be taken 0 (predose) and 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24 and 36 hr post-dose

• Terminal half-life (t1/2)

  Samples will be taken 0 (predose) and 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24 and 36 hr post-dose

• Rate constant of elimination (λz)

  Samples will be taken 0 (predose) and 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24 and 36 hr post-dose

• Apparent total body clearance (CL/f)

  Samples will be taken 0 (predose) and 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24 and 36 hr post-dose

Study Arms (4)

Elantan SR 60 mg fed

EXPERIMENTAL

Elantan SR 60 mg is orally administered on Day 1 of treatment period 1 for Fed group 2 and on Day 1 of treatment period 2 for Fed group 1.

Drug: Elantan SR 60 mg

Imdur SR 60 mg fed

EXPERIMENTAL

Imdur SR 60 mg is orally administered on Day 1 of treatment period 1 for Fed group 1 and on Day 1 of treatment period 2 for Fed group 2.

Drug: Imdur SR 60 mg

Elantan SR 60 mg fasted

EXPERIMENTAL

Elantan SR 60 mg is orally administered on Day 1 of treatment period 1 for Fasted group 2 and on Day 1 of treatment period 2 for Fasted group 1.

Drug: Elantan SR 60 mg

Imdur SR 60 mg fasted

EXPERIMENTAL

Imdur SR 60 mg is orally administered on Day 1 of treatment period 1 for Fasted group 1 and on Day 1 of treatment period 2 for Fasted group 2.

Drug: Imdur SR 60 mg

Interventions

Elantan SR 60 mg DRUG

* Trade Name: Elantan * Active Substance: Isosorbide 5-mononitrate * Pharmaceutical form: Tablet * Concentration: 60 mg * Route of Administration: Oral administration

Also known as: Isosorbide 5-mononitrate

Elantan SR 60 mg fasted; Elantan SR 60 mg fed

Imdur SR 60 mg DRUG

* Trade Name: Elantan * Active Substance: Isosorbide 5-mononitrate * Pharmaceutical form: Tablet * Concentration: 60 mg * Route of Administration: Oral administration

Also known as: Isosorbide 5-mononitrate

Imdur SR 60 mg fasted; Imdur SR 60 mg fed

Eligibility Criteria

• Age: 19 Years - 55 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• An Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved written informed consent is signed and dated by the subject
• Subject is considered reliable and capable of adhering to the protocol (eg, able to understand and complete the schedule of study assessment), visit schedule or medication intake according to the judgment of the investigator
• Subject is healthy Korean male, 19-55 years of age
• Subject is of normal body weight as determined by a body mass index between 18.5 kg/m\^2 and 24.9 kg/m\^2
• Sitting blood pressure within the following range: SBP (Systolic Blood Pressure), 90-139 mmHg; DBP (Diastolic Blood Pressure ), 50-89 mmHg
• Subject has no abnormal symptom in a physical examination without congenital or chronic disease

You may not qualify if:

• Subject has previously participated in this study or subject has previously been assigned to treatment in a study of the medication under investigation in this study
• Subject has participated in another study of an investigational medication (or a medical device) within the last 90 days or is currently participating in another study of an investigational medication (or a medical device)
• Subject has a history of chronic alcohol or drug abuse within the last 6 months
• Subject has any medical or psychiatric condition that, in the opinion of the investigator, could jeopardize or would compromise the subject's ability to participate in this study
• Subject has a known hypersensitivity to nitrate or to any components of the investigational medicinal product or reference drugs as stated in this protocol
• Subject has the history or present condition of cardiovascular diseases, like acute circulatory failure (shock, vascular collapse), very low BP, acute myocardial infarction with low filling pressures, arrhythmia, left heart failure with low filling pressures, hypotension, acute attacks of angina, constrictive pericarditis, hypertrophic obstructive cardiomyopathy, cardiac tamponade, aortic valve and/or mitral valve stenosis
• Subject has the history or present condition of severe anemia, head trauma, cerebral haemorrhage, hematopenia, severe cerebrovascular insufficiency, glaucoma, gastrointestinal disorder, neurological abnormalities, hepatic disorder, renal, pulmonary or metabolic diseases
• Subject use a phosphodiesterase 5 inhibitor (sildenafil, tadalafil and vardenafil)
• Symptomatic or asymptomatic orthostatic hypotension at screening defined as a 20 mmHg or more decrease in systolic pressure, or 10 mmHg or more decrease in diastolic pressure after 1 and 3 minutes standing with the arm relaxed at the side (time zero begins after the subject is upright). 5 minutes of supine rest is used as baseline
• Subject has the family or personal history of abnormal bleeding
• Subject had clinically relevant out of range values for hematology and clinical chemistry parameters. However, in agreement with the sponsor, the Investigator may include a subject having values outside the accepted range if, in his/her opinion, these values are of no clinical significance and justification is given
• Subject had any clinically relevant abnormality in physical examination
• Subject has made a blood donation or had a comparable blood loss (\>400ml) within the last 3 months prior to the first day of dosing
• Any clinical conditions that in the opinion of the Investigator would make the subject unsuitable for the study
• Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption due to the presence of lactose

Sponsors & Collaborators

• UCB Korea Co., Ltd.: lead
• Seoul Pharma Laboratories Inc.: collaborator

Study Sites (1)

1

Jeollabuk-do, South Korea

Location

Related Publications (1)

• Jin C, Jeon JY, Im YJ, Jeong JA, Kim Y, Chae SW, Bentz J, Kumke T, Kim MG. Pharmacokinetic properties of isosorbide-5-mononitrate under fasting and fed conditions in healthy male subjects. Int J Clin Pharmacol Ther. 2015 Jan;53(1):97-106. doi: 10.5414/CP202169.

  PMID: 25492848 DERIVED

MeSH Terms

Interventions

Isosorbide

Intervention Hierarchy (Ancestors)

Sorbitol; Sugar Alcohols; Alcohols; Organic Chemicals; Carbohydrates

Study Officials

• UCB Clinical Trial Call Center

  +1 877 822 9493

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 28, 2014
• First Posted: April 2, 2014
• Study Start: June 1, 2011
• Primary Completion: July 1, 2011
• Study Completion: July 1, 2011
• Last Updated: April 17, 2014

Record last verified: 2014-04

Locations

KR (1)