A Bioequivalence Study of Isosorbide-5-Mononitrate Extended-Release Tablets Under Fed Conditions in Healthy Subjects

NCT03557580 | Completed Phase 1

• 1 other identifier: QL-YK1-039-Y01
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this trial is to compare the pharmacokinetic characteristics of two isosorbide -5 -mononitrate extended -release tablets 40 mg of Qilu Pharmaceutical Co., Ltd and ISMO Retard (isosorbide -5 -mononitrate extended -release tablet) 40 mg, distributed by RIEMSER Pharma GmbH. Primary endpoints are Cmax, AUC(0-t) and AUC(0-inf). Secondary endpoints are Tmax, t1/2 and λz.

Conditions

Bioequivalence

Outcome Measures

Primary Outcomes (3)

• Cmax

  Maximum plasma Capecitabine concentration

  Pre-dose and 0.5, 1.0, 2.0, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 6.5, 7.0, 7.5, 8.0, 9.0, 10.0, 12.0, 24.0 36.0 and 48.0 hr post-dose

• AUC0-t

  The area under the plasma concentration time curve from zero to the last measurable concentration.

  Pre-dose and 0.5, 1.0, 2.0, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 6.5, 7.0, 7.5, 8.0, 9.0, 10.0, 12.0, 24.0 36.0 and 48.0 hr post-dose

• AUC0-∞

  The area under the plasma concentration time curve from zero to infinity.

  Pre-dose and 0.5, 1.0, 2.0, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 6.5, 7.0, 7.5, 8.0, 9.0, 10.0, 12.0, 24.0 36.0 and 48.0 hr post-dose

Secondary Outcomes (3)

• Tmax

  Pre-dose and 0.5, 1.0, 2.0, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 6.5, 7.0, 7.5, 8.0, 9.0, 10.0, 12.0, 24.0 36.0 and 48.0 hr post-dose

• Kel

  Pre-dose and 0.5, 1.0, 2.0, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 6.5, 7.0, 7.5, 8.0, 9.0, 10.0, 12.0, 24.0 36.0 and 48.0 hr post-dose

• t½

  Pre-dose and 0.5, 1.0, 2.0, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 6.5, 7.0, 7.5, 8.0, 9.0, 10.0, 12.0, 24.0 36.0 and 48.0 hr post-dose

Study Arms (3)

IS-5-MN R

ACTIVE COMPARATOR

Isosorbide-5-mononitrate extended-release tablet, Single oral dose 40mg

Drug: IS-5-MN R

IS-5-MN T1

EXPERIMENTAL

Isosorbide-5-mononitrate extended-release tablet, Single oral dose 40mg

Drug: IS-5-MN T1

IS-5-MN T2

EXPERIMENTAL

Isosorbide-5-mononitrate extended-release tablet, Single oral dose 40mg

Drug: IS-5-MN T2

Interventions

IS-5-MN R DRUG

single orally dose under fed conditions on day 1 of treatment period 1 for group 1, on day 1 of treatment period 2 for group 2, on day 1 of treatment period 3 for group 3.

Also known as: ISMO Retard, IS-5-MN

IS-5-MN R

IS-5-MN T1 DRUG

single orally dose under fed conditions on day 1 of treatment period 2 for group 1, on day 1 of treatment period 3 for group 2, on day 1 of treatment period 1 for group 3.

Also known as: IS-5-MN

IS-5-MN T1

IS-5-MN T2 DRUG

single orally dose under fed conditions on day 1 of treatment period 3 for group 1, on day 1 of treatment period 1 for group 2, on day 1 of treatment period 2 for group 3.

Also known as: IS-5-MN

IS-5-MN T2

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Subjects should read, sign, and date an Informed Consent Form under the premise of fully understanding of this study including risks and requirements; are unable to follow the rules of this study, prior to any study procedures;
• Healthy male or non-pregnant, non-lactating female of age between 18 to 50 years (both inclusive);
• Body weight ≥ 50 kg for male and 45 kg for female, body mass index (BMI) within 19.0-25.0 Kg/m2;
• Subject (including male subject) has no fertility plan within the future 3 months and take reliable contraceptive (physical);
• Subject must agree to use an acceptable method of birth control such as sexual abstinence or barrier method of contraception from screening until 3 months after last dose of study drug;
• Subject is considered reliable and capable of adhering to the protocol visit schedule or medication intake according to the judgment of the investigator.

You may not qualify if:

• Subject has allergic constitution or hypersensitivity to the active substance or to isosorbide dinitrate, or rare hereditary problems of galactose intolerance or fructose intolerance, the Lapp lactase deficiency, glucose - galactose malabsorption or sucrase - isomaltase insufficiency.
• Subject has dysphagia or any disorder that may interfere with drug absorption, distribution, metabolism, or excretion, e.g. gastrointestinal, liver, kidney conditions.
• Subject has alcoholism history or drank excessive alcohol within 6 months prior to the study (who drinking more than 21 units of alcohol per week, 1 unit = 360 mL beer (5%) = 45 mL spirit (40%) = 150 mL red-wine (12%)), positive test results for breath alcohol test at baseline, or cannot stop alcohol intake during study.
• Subject smoking more than 5 cigarettes/nicotine-containing products a day within 3 months prior to screening, or refusing to abstain from smoking or consumption of tobacco products during the study.
• Subject has significant change in diet or exercise habits within 3 months prior to screening.
• Subject has any food restrictions or intolerance.
• Subject has hospitalization history or surgery within 3 months prior to screening.
• Subject has made a blood donation or had a comparable blood loss (\>400ml) within 3 months prior to screening.
• Subject has participated in another study of an investigational medication within the last 3 months, or taking any drugs known to have a well established toxic potential to major organs within 3 months prior to study administration.
• Subject with clinically significant blood, kidneys, endocrine, gastrointestinal, respiratory, cardiovascular, hepatic, psychiatric, immunological and neurological disease.
• Subject in cases of marked low blood pressure (BP ≤ 90 mmHg systolic), aortic/mitral valve stenosis, severe anaemia, glaucoma, or using a phosphodiesterase 5 inhibitor.
• Subject has history of drug abuse within the past 5 years, using any recreational drugs within 3 months prior to screening, or positive test results for urine drug scan.
• Female subject in lactation period, or has positive pregnancy test result, or had unprotected sexual intercourse within 14 days prior to first drug administration, or refusing to take non-pharmacological contraception (such as condoms, intrauterine devices, contraceptive rings, ligation, etc.).
• Subject with clinically significant positive test results for: HIV, Hepatitis B surface antigen, Hepatitis C antibody or treponema pallidum.
• Subject used any drugs known to induce or inhibit hepatic drug metabolism within 28 days prior to study administration.

Sponsors & Collaborators

• Qilu Pharmaceutical Co., Ltd.: lead

Study Sites (1)

Qingyuan People's Hospital

Qingyuan, China

Location

MeSH Terms

Interventions

Isosorbide

Intervention Hierarchy (Ancestors)

Sorbitol; Sugar Alcohols; Alcohols; Organic Chemicals; Carbohydrates

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: June 4, 2018
• First Posted: June 15, 2018
• Study Start: April 17, 2018
• Primary Completion: May 6, 2018
• Study Completion: May 18, 2018
• Last Updated: June 15, 2018

Record last verified: 2018-06

Locations

CN (1)