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Bioequivalence Study of Clopidogrel 75 mg in Two Tablet Formulations Relative to Reference Tablet in Healthy Subjects

3 maggio 2017 aggiornato da: GlaxoSmithKline

An Open-label, Randomised, Single-dose, Three-way Cross Over, Six Sequence Study to Determine the Relative Bioavailability of Clopidogrel 75mg From Two Tablet Formulations of SB224326 Relative to One 75mg Reference Tablet of Clopidogrel in Healthy Adult Human Subjects Under Fasting Conditions

Clopidogrel is a potent anti-thrombotic drug that inhibits adenosine diphosphate (ADP)-induced platelet aggregation. This is an open-label, randomized, single dose, three-way cross over, six sequence study to investigate the relative bioavailability of two 75 milligrams (mg) clopidogrel tablet formulations (clopidogrel SB224326 test formulation 1 [Clop F1] and clopidogrel SB224326 test formulation 2 [Clop F2]) compared with the reference product (innovator) in healthy human subjects. A total of 18 healthy human subjects will be randomized, such that approximately 14 evaluable subjects complete the study. Total duration in the study for each subject will be approximately 8 weeks from screening to the follow-up visit.

Panoramica dello studio

Stato

Completato

Tipo di studio

Interventistico

Iscrizione (Effettivo)

18

Fase

  • Fase 1

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Luoghi di studio

      • Telangana, India, 500 013
        • GSK Investigational Site

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

Da 18 anni a 65 anni (Adulto, Adulto più anziano)

Accetta volontari sani

Sessi ammissibili allo studio

Tutto

Descrizione

Inclusion Criteria:

  • Adult subjects aged between 18 and 65 years of age inclusive, at the time of signing the informed consent.
  • Healthy, non-smoker, as determined by the investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring.
  • A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or exclusion criteria, outside the reference range for the population being studied may be included only if the investigator in consultation with the Medical Monitor if required, agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
  • Body weight >=50 kilograms (kg) and Body mass index (BMI) within the range 19 - 24.9 kg/square meter (m^2) (inclusive).
  • Healthy male or female subjects: MALES: Male subjects with female partners of child bearing potential must comply with the following contraception requirements from the time of first dose of study medication until 24 hours after the last dose of study medication: a) Vasectomy with documentation of azoospermia. b) Male condom plus partner use of one of the contraceptive following options: Contraceptive subdermal implant, Intrauterine device or intrauterine system, Oral Contraceptive, either combined or progestogen alone, Injectable progestogen, Contraceptive vaginal ring, Percutaneous contraceptive patches, This is an all inclusive list of those methods that meet the GlaxoSmithKline (GSK) definition of highly effective: having a failure rate of less than 1% per year when used consistently and, correctly and, when applicable, in accordance with the product label. For non-product methods (e.g. male sterility), the investigator determines what is consistent and correct use. The GSK definition is based on the definition provided by International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). The investigator is responsible for ensuring that subjects understand how to properly use these methods of contraception. FEMALES: Eligible to participate, if she is not pregnant (as confirmed by a negative serum human chorionic gonadotrophin [hCG] test), not lactating, and at least one of the following conditions applies: a) Non-reproductive potential defined as: Pre-menopausal females with one of the following: Documented tubal ligation, Documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion, Hysterectomy, Documented Bilateral Oophorectomy, Postmenopausal defined as 12 months of spontaneous amenorrhea (in questionable cases a blood sample with simultaneous follicle stimulating hormone [FSH] and estradiol levels consistent with menopause). Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the highly effective contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrolment. b) Reproductive potential and agrees to follow one of the options listed below in the Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential (FRP) from 30 days prior to the first dose of study medication and until 24 hours after the last dose of study medication and completion of the follow-up visit.
  • Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.

Exclusion Criteria:

  • Innovator product contains lactose and subjects with lactose intolerance should not be included.
  • Alanine aminotransferase (ALT) and bilirubin >1.5xupper limit of normal (ULN) (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
  • Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
  • Corrected QT interval (QTc) > 450 milliseconds (msec) NOTES: The QTc is the QT interval corrected for heart rate according to Bazett's formula (QTcB), Fridericia's formula (QTcF), and/or another method, machine-read or manually over-read. The specific formula that will be used to determine eligibility and discontinuation for an individual subject should be determined prior to initiation of the study. In other words, several different formulae cannot be used to calculate the QTc for an individual subject and then the lowest QTc value used to include or discontinue the subject from the trial. For purposes of data analysis, QTcB, QTcF, another QT correction formula, or a composite of available values of QTc will be used.
  • The following medications increase risk of bleeding: Nonsteroidal anti-inflammatory drugs (NSAIDs), warfarin, selective serotonin and serotonin norepinephrine reuptake inhibitors (SSRIs, SNRIs).
  • Proton pump inhibitors: some drugs from this class have an inhibitory effect on the formation of clopidogrel active metabolite.
  • History of regular alcohol consumption within 6 months of the study defined as: An average weekly intake of >21 units for males or >14 units for females. One unit is equivalent to 8 grams (g) of alcohol: a half-pint (~240 milliliter [mL]) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
  • Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening.
  • History of sensitivity to heparin or heparin-induced thrombocytopenia.
  • History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or Medical Monitor, contraindicates their participation.
  • Active pathological bleeding, such as peptic ulcer or intra cranial haemorrhage
  • Presence of hepatitis B surface antigen (HBsAg), positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study treatment.
  • A positive pre-study drug/alcohol screen.
  • A positive test for Human Immunodeficiency Virus (HIV) antibody.
  • Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 90 day period.
  • The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 90 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
  • Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
  • Gastrointestinal disease or with gastrointestinal surgical history which can affect the absorption of the investigational drug.
  • Any symptoms with a systolic blood pressure (BP) <95 millimeter of mercury (mmHg)

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

  • Scopo principale: Scienza basilare
  • Assegnazione: Randomizzato
  • Modello interventistico: Assegnazione incrociata
  • Mascheramento: Nessuno (etichetta aperta)

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Sperimentale: Treatment Sequence A (Innovator) - B (Clop F1) - C (Clop F2)
Subjects will receive a single 75 mg tablet of reference clopidogrel (Treatment A) in treatment period 1, 75 mg tablet Clop F1 (Treatment B) in treatment period 2, and 75 mg tablet Clop F2 (Treatment C) in treatment period 3 under fasting conditions. Each treatment period will be separated by 7-14 days of washout Period.
A single oral dose of clopidogrel (bisulfate) 75 mg tablet will be administered with approximately 240 mL water in fasted state.
A single oral dose of clopidogrel (bisulfate) 75 mg tablet will be administered with approximately 240 mL water in fasted state.
A single oral dose of clopidogrel (bisulfate) 75 mg tablet will be administered with approximately 240 mL water in fasted state.
Sperimentale: Treatment Sequence A(Innovator) -C(Clop F2)-B (Clop F1)
Subjects will receive a single 75 mg tablet of reference clopidogrel (Treatment A) in treatment period 1, 75 mg tablet Clop F2 (Treatment C) in treatment period 2, and 75 mg tablet Clop F1 (Treatment B) in treatment period 3 under fasting conditions. Each treatment period will be separated by 7-14 days of washout Period.
A single oral dose of clopidogrel (bisulfate) 75 mg tablet will be administered with approximately 240 mL water in fasted state.
A single oral dose of clopidogrel (bisulfate) 75 mg tablet will be administered with approximately 240 mL water in fasted state.
A single oral dose of clopidogrel (bisulfate) 75 mg tablet will be administered with approximately 240 mL water in fasted state.
Sperimentale: Treatment Sequence B (Clop F1) - A (Innovator) - C (Clop F2)
Subjects will receive a single 75 mg tablet Clop F1 (Treatment B) in treatment period 1, 75 mg tablet of reference clopidogrel (Treatment A) in treatment period 2, and 75 mg tablet Clop F2 (Treatment C) in treatment period 3 under fasting conditions. Each treatment period will be separated by 7-14 days of washout Period.
A single oral dose of clopidogrel (bisulfate) 75 mg tablet will be administered with approximately 240 mL water in fasted state.
A single oral dose of clopidogrel (bisulfate) 75 mg tablet will be administered with approximately 240 mL water in fasted state.
A single oral dose of clopidogrel (bisulfate) 75 mg tablet will be administered with approximately 240 mL water in fasted state.
Sperimentale: Treatment Sequence B (Clop F1) - C (Clop F2) - A (Innovator)
Subjects will receive a single 75 mg tablet Clop F1 (Treatment B) in treatment period 1, 75 mg tablet Clop F2 (Treatment C) in treatment period 2, and 75 mg tablet of reference clopidogrel (Treatment A) in treatment period 3 under fasting conditions. Each treatment period will be separated by 7-14 days of washout Period.
A single oral dose of clopidogrel (bisulfate) 75 mg tablet will be administered with approximately 240 mL water in fasted state.
A single oral dose of clopidogrel (bisulfate) 75 mg tablet will be administered with approximately 240 mL water in fasted state.
A single oral dose of clopidogrel (bisulfate) 75 mg tablet will be administered with approximately 240 mL water in fasted state.
Sperimentale: Treatment Sequence C (Clop F2) - A (Innovator) - B (Clop F1)
Subjects will receive a single 75 mg tablet Clop F2 (Treatment C) in treatment period 1, 75 mg tablet of reference clopidogrel (Treatment A) in treatment period 2, and 75 mg tablet Clop F1 (Treatment B) in treatment period 3 under fasting conditions. Each treatment period will be separated by 7-14 days of washout Period.
A single oral dose of clopidogrel (bisulfate) 75 mg tablet will be administered with approximately 240 mL water in fasted state.
A single oral dose of clopidogrel (bisulfate) 75 mg tablet will be administered with approximately 240 mL water in fasted state.
A single oral dose of clopidogrel (bisulfate) 75 mg tablet will be administered with approximately 240 mL water in fasted state.
Sperimentale: Treatment Sequence C (Clop F2) - B (Clop F1) - A (Innovator)
Subjects will receive a single 75 mg tablet Clop F2 (Treatment C) in treatment period 1, 75 mg tablet Clop F1 (Treatment B) in treatment period 2, and 75 mg tablet of reference clopidogrel (Treatment A) in treatment period 3 under fasting conditions. Each treatment period will be separated by 7-14 days of washout Period.
A single oral dose of clopidogrel (bisulfate) 75 mg tablet will be administered with approximately 240 mL water in fasted state.
A single oral dose of clopidogrel (bisulfate) 75 mg tablet will be administered with approximately 240 mL water in fasted state.
A single oral dose of clopidogrel (bisulfate) 75 mg tablet will be administered with approximately 240 mL water in fasted state.

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Composite of plasma pharmacokinetic (PK) parameters: AUC(0 ∞), AUC(0 t) and Cmax
Lasso di tempo: Day 1: pre-dose, 0.25, 0.5, 0.75, 1.00, 1.33, 1.67, 2, 2.5, 3.00, 4.00, 5.00, 6.00, 8.00, 10.00, 12.00, 16.00, 24.00 (Day 2) hours post-dose of each treatment period
The following PK parameters were measured: area under the plasma concentration-time curve from time zero to infinity (AUC[0 ∞]), area under the plasma concentration-time curve from time zero to last time point with measurable concentration (AUC[0 t]) and maximum observed plasma concentration (Cmax)
Day 1: pre-dose, 0.25, 0.5, 0.75, 1.00, 1.33, 1.67, 2, 2.5, 3.00, 4.00, 5.00, 6.00, 8.00, 10.00, 12.00, 16.00, 24.00 (Day 2) hours post-dose of each treatment period

Misure di risultato secondarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Composite of plasma PK parameters: time of occurrence of Cmax (tmax), percentage of AUC(0 ∞) obtained by extrapolation (%AUCex) and terminal phase half-life (t1/2)
Lasso di tempo: Day 1: pre-dose, 0.25, 0.5, 0.75, 1.00, 1.33, 1.67, 2, 2.5, 3.00, 4.00, 5.00, 6.00, 8.00, 10.00, 12.00, 16.00, 24.00 (Day 2) hours post-dose of each treatment period
Pre-dose PK blood samples will be collected within 60 minutes prior to dose. Post dose blood samples will be collected within 2 minutes.
Day 1: pre-dose, 0.25, 0.5, 0.75, 1.00, 1.33, 1.67, 2, 2.5, 3.00, 4.00, 5.00, 6.00, 8.00, 10.00, 12.00, 16.00, 24.00 (Day 2) hours post-dose of each treatment period
Blood pressure as a measure of safety and tolerability
Lasso di tempo: Up to 8 weeks
Blood pressure will be measured at predose, 0.50, 1.00, 2.00, 4.00, and 24.00 hours post-dose. Post dose blood pressure to be taken plus or minus 30 minutes of each timepoint.
Up to 8 weeks
Pulse rate as a measure of safety and tolerability
Lasso di tempo: Up to 8 weeks
Pulse rate will be measured at predose, 0.50, 1.00, 2.00, 4.00, and 24.00 hours post-dose. Post dose pulse rate to be taken plus or minus 30 minutes of each timepoint.
Up to 8 weeks
Number of subjects with adverse events and serious adverse events
Lasso di tempo: From start of study medication until follow up (Up to 5 weeks)
An AE is any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE was defined as any untoward medical occurrence that, at any dose, resulted in death, was life threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity, was a congenital anomaly/birth defect, or was an event of possible drug-induced liver injury.
From start of study medication until follow up (Up to 5 weeks)
Composite of hematology parameters as a measure of safety
Lasso di tempo: Up to 8 weeks
The following hematology assessments will be performed: platelet count, red blood cell (RBC) count, hemoglobin, hematocrit, white blood cells (WBC) (absolute), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), neutrophils, lymphocytes, monocytes, eosinophils, and basophils.
Up to 8 weeks
Composite of clinical chemistry parameters as a measure of safety
Lasso di tempo: Up to 8 weeks
The following clinical chemistry assessments will be performed: blood urea nitrogen (BUN), creatinine, fasting glucose, potassium, sodium, calcium, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, total and direct bilirubin, total protein, and albumin.
Up to 8 weeks
Composite of urinalysis parameters as measured by dipstick method and microscopic examination
Lasso di tempo: Up to 8 weeks
Dipstick method will be used to measure pH, glucose, protein, blood and ketones. Microscopic examination will be performed if blood or protein is abnormal.
Up to 8 weeks

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio (Effettivo)

4 settembre 2015

Completamento primario (Effettivo)

24 settembre 2015

Completamento dello studio (Effettivo)

24 settembre 2015

Date di iscrizione allo studio

Primo inviato

9 luglio 2015

Primo inviato che soddisfa i criteri di controllo qualità

16 luglio 2015

Primo Inserito (Stima)

20 luglio 2015

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Effettivo)

8 maggio 2017

Ultimo aggiornamento inviato che soddisfa i criteri QC

3 maggio 2017

Ultimo verificato

1 maggio 2017

Maggiori informazioni

Termini relativi a questo studio

Termini MeSH pertinenti aggiuntivi

Altri numeri di identificazione dello studio

  • 200096

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

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