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

Condition(s) targeted: Healthy

Intervention: Elantan SR 60 mg (Drug); Imdur SR 60 mg (Drug)

Phase: Phase 1

Status: Completed

Sponsored by: Korea UCB Co., Ltd.

Official(s) and/or principal investigator(s):
UCB Clinical Trial Call Center, Study Director, Affiliation: +1 877 822 9493

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

Official title: A Randomized, Open-label, One Dose, 2-way Crossover Study to Evaluate the Bioequivalence of Elantan SR* 60 mg in Comparison With Imdur SR* 60 mg Under Fasted and Fed Conditions in Healthy Korean Male Subjects (*Sustained Release)

Study design: Allocation: Randomized, Endpoint Classification: Bio-equivalence Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome:

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

Maximum Observed Plasma Concentration (Cmax)

Secondary outcome:

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

Time to reach a maximum plasma concentration (tmax)

Terminal half-life (t1/2)

Rate constant of elimination (λz)

Apparent total body clearance (CL/f)

Apparent volume of distribution (Vz/F)

AUC % extrapolation

Percentage of subjects with at least one Treatment-emergent Adverse Event (TEAE) from the Day 1 of the first treatment period until Safety Follow Up visit

Detailed description: This study is to evaluate the bioequivalence of Elantan SR 60 mg compared to Imdur SR 60 mg in sixty healthy Korean male subjects. Thirty subjects will be participating in a fasted state and other thirty subjects will be in a fed state. Elantan SR 60 mg and Imdur 60 mg are two formulations of Isosorbide 5-mononitrate.

Minimum age: 19 Years. Maximum age: 55 Years. Gender(s): Male.

Criteria:

Inclusion Criteria:

- 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 Exclusion Criteria:

- 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

- Subjects who have taken drug products that are enzyme inducers, such as barbiturates,

or inhibitors; or who drank excessive alcohol within one month prior to the initiation of the BE (Bioequivalence) study

- Subjects who have taken drug products that could influence the results of the BE

study within 10 days before the initiation of the BE study

1, Jeollabuk-do, Korea, Republic of

Starting date: June 2011
Last updated: April 16, 2014