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Glucophage Immediate Release (GIR) China Bioequivalence Study

3 de mayo de 2019 actualizado por: Merck KGaA, Darmstadt, Germany

A Randomized, Open-label, 2-Way-Crossover Study Assessing the Bioequivalence Between Single Doses of 500 mg Glucophage Immediate Release (GIR) Tablets (Sino-American Shanghai Squibb Pharmaceuticals Ltd./ Manufactured in China) and 500 mg GIR Tablets (Merck Santé s.a.s. in Semoy/ Manufactured in France) Under Fed and Fasted State in Two Groups of Healthy Subjects

The study will assess the bioequivalence between single doses of glucophage immediate release (GIR) test tablets and GIR reference tablets under fed and fasted state in healthy subjects.

Descripción general del estudio

Estado

Terminado

Condiciones

Intervención / Tratamiento

Tipo de estudio

Intervencionista

Inscripción (Actual)

44

Fase

  • Fase 1

Contactos y Ubicaciones

Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.

Ubicaciones de estudio

      • Beijing, Porcelana, 100053
        • Xuanwu Hospital

Criterios de participación

Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.

Criterio de elegibilidad

Edades elegibles para estudiar

18 años a 55 años (Adulto)

Acepta Voluntarios Saludables

No

Géneros elegibles para el estudio

Todos

Descripción

Inclusion Criteria:

  • Participants had given written informed consent before any trial-related activities
  • Chinese male and female participants (at least 1/4 of each gender per trial group)
  • Aged between 18 and 55 years, inclusive
  • Weighed: 50 to 80 kilogram (kg); Body mass index (BMI): 18 to 30 kg per meter square
  • Nonsmoker since at least 3 months
  • Good physical and mental health status, determined on the basis of the medical history and a physical examination
  • All values for biochemistry and hematology tests of blood and urine within the normal range or showied no clinically relevant deviation as judged by the Investigator
  • Electrocardiogram recording (12-lead ECG) without signs of clinically relevant pathology was judged by the Investigator
  • Vital signs (blood pressure, pulse, body temperature, and respiration) in sitting position within the normal range or showing no clinically relevant deviation was judged by the Investigator
  • All women of childbearing potential (WOCBP) who were not nursing, were not pregnant, and were using highly effective methods of birth control
  • Negative screen for alcohol and drugs of abuse (cannabis, benzodiazepines, barbiturates, opiates, cocaine, and methyl amphetamine) were screened at and on admission
  • Negative screen for hepatitis A virus (HAV) antibodies, hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibodies, human immunodeficiency virus (HIV) antibodies, and Treponema pallidum (TP) antibodies

Exclusion Criteria:

  • Participation in a clinical trial within 90 days prior to first drug administration
  • Blood donation (equal or more than 500 milliliter [mL]) or significant blood loss within 90 days prior to first drug administration
  • Any surgical or medical condition, including findings in the medical history or in the pretrial assessments, or any other significant disease, that in the opinion of the Investigator, constitutes a risk or a contraindication for the participation of the participant in the trial or that could interfere with the trial objectives, conducted or evaluated
  • History of surgery of the gastrointestinal tract which could influence the gastrointestinal absorption and/or motility according to the Investigator's opinion
  • History or presence of relevant liver diseases or hepatic dysfunction Allergy: ascertained or presumptive hypersensitivity to the active drug substance and/or formulations' ingredients; history of anaphylaxis to drugs or allergic reactions in general, which the Investigator considered affectted the outcome of the trial
  • Receipt of any prescription or nonprescription medication within 2 weeks before the first IMP administration, including multivitamins and herbal products (example, St John's Wort, or traditional Chinese medicines), except paracetamol
  • Renal failure or renal dysfunction (creatinine clearance < 80 mL/minute) as assessed by using the estimated measure with the Modification of Diet in Renal Disease (MDRD) equation
  • Known lack of participant compliance or inability to communicate or cooperate with the Investigator (example, language problem and poor mental status)
  • Nonacceptance of trial high-fat breakfast (example, vegetarians, vegans, and participants followed special diets)
  • Consumption of large quantities of methyl xanthine-containing beverages (> 5 cups of coffee/day or equivalent)
  • Consumption of grapefruit, cranberry or juices of these fruits, from 14 days prior to drug administration until collection of the last pharmacokinetic sample in Period 2
  • Any contraindication to Glucophage
  • Abnormal and clinically significant chest X-ray finding at screening

Plan de estudios

Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.

¿Cómo está diseñado el estudio?

Detalles de diseño

  • Propósito principal: Otro
  • Asignación: Aleatorizado
  • Modelo Intervencionista: Asignación cruzada
  • Enmascaramiento: Ninguno (etiqueta abierta)

Armas e Intervenciones

Grupo de participantes/brazo
Intervención / Tratamiento
Experimental: First Test GIR (Fasting), Then Reference GIR (Fasting)
Participants received a single oral dose of 500 milligram (mg) of test Glucophage Immediate Release (GIR) tablet Sino-American Shanghai Squibb (SASS)/China) on Day 1 in treatment period 1 followed by a single oral dose of 500 mg reference GIR (Merck Santé in Semoy (MSS)/France) on Day 8 in treatment period 2 under fasting condition. There was a wash-out period of 7 days between each treatment period.
Participants received 500 milligrams (mg) test GIR in fasting or fed state on either Day 1 (Treatment Period 1) or Day 8 (Treatment Period 2).
Otros nombres:
  • Metformina
Participants received 500 mg reference GIR in fasting or fed state on either Day 1 (Treatment Period 1) or Day 8 (Treatment Period 2).
Otros nombres:
  • Metformina
Experimental: First Reference GIR (Fasting), Then Test GIR (Fasting)
Participants received a single oral dose of 500 mg of reference GIR tablet (MSS/France) on Day 1 in treatment period 1 followed by a single oral dose of 500 mg test GIR (SASS/China) on Day 8 in treatment period 2 under fasting condition. There was a wash-out period of 7 days between each treatment period.
Participants received 500 milligrams (mg) test GIR in fasting or fed state on either Day 1 (Treatment Period 1) or Day 8 (Treatment Period 2).
Otros nombres:
  • Metformina
Participants received 500 mg reference GIR in fasting or fed state on either Day 1 (Treatment Period 1) or Day 8 (Treatment Period 2).
Otros nombres:
  • Metformina
Experimental: First Test GIR (Fed), Then Reference GIR (Fed)
Participants received a single oral dose of 500 mg of test GIR tablet (SASS/ China) on Day 1 in treatment period 1 followed by a single oral dose of 500 mg reference GIR (MSS/France) on Day 8 in treatment period 2 under fed condition. There was a wash-out period of 7 days between each treatment period.
Participants received 500 milligrams (mg) test GIR in fasting or fed state on either Day 1 (Treatment Period 1) or Day 8 (Treatment Period 2).
Otros nombres:
  • Metformina
Participants received 500 mg reference GIR in fasting or fed state on either Day 1 (Treatment Period 1) or Day 8 (Treatment Period 2).
Otros nombres:
  • Metformina
Experimental: First Reference GIR (Fed), Then Test GIR (Fed)
Participants received a single oral dose of 500 mg of reference GIR tablet (MSS/ France) on Day 1 in treatment period 1 followed by a single oral dose of 500 mg test GIR (SASS/China) on Day 8 in treatment period 2 under fed condition. There was a wash-out period of 7 days between each treatment period.
Participants received 500 milligrams (mg) test GIR in fasting or fed state on either Day 1 (Treatment Period 1) or Day 8 (Treatment Period 2).
Otros nombres:
  • Metformina
Participants received 500 mg reference GIR in fasting or fed state on either Day 1 (Treatment Period 1) or Day 8 (Treatment Period 2).
Otros nombres:
  • Metformina

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC 0-t) of Metformin (GIR Tablet Active Ingredient)
Periodo de tiempo: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; 48 hours post-dose on Day 3
Area under the plasma concentration vs time curve from time zero to the last sampling time t at which the concentration was at or above the lower limit of quantification (LLQ). AUC0-t was to be calculated according to the mixed log-linear trapezoidal rule.
Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; 48 hours post-dose on Day 3
Maximum Observed Plasma Concentration (Cmax) of Metformin (GIR Tablet Active Ingredient)
Periodo de tiempo: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; 48 hours post-dose on Day 3
Pharmacokinetic (PK) parameter Cmax was obtained directly from the concentration versus time curve.
Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; 48 hours post-dose on Day 3

Medidas de resultado secundarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Time to Reach Maximum Plasma Concentration of Metformin (GIR Tablet Active Ingredient)
Periodo de tiempo: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; 48 hours post-dose on Day 3
Time to reach the maximum plasma concentration (Tmax) was obtained directly from the concentration versus time curve.
Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; 48 hours post-dose on Day 3
Apparent Terminal Half-Life (t1/2) of Metformin (GIR Tablet Active Ingredient)
Periodo de tiempo: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; 48 hours post-dose on Day 3
Terminal half-life is the time measured for the concentration to decrease by one half. Terminal half-life calculated by natural log 2 divided by λz.
Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; 48 hours post-dose on Day 3
Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity (AUCinf) of Metformin (GIR Tablet Active Ingredient)
Periodo de tiempo: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; 48 hours post-dose on Day 3
AUC0-inf was calculated by combining AUC0-t and AUCextra. AUC extra represents an extrapolated value obtained by Clast/ λz, where Clast is the calculated plasma concentration at the last sampling time point at which the measured plasma concentration is at or above the Lower Limit of quantification (LLQ) and λz is the apparent terminal rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal log-linear phase.
Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; 48 hours post-dose on Day 3
Area Under the Plasma Concentration-Time Curve From Time Tlast Extrapolated to Infinity (AUCextra) of Metformin (GIR Tablet Active Ingredient)
Periodo de tiempo: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; 48 hours post-dose on Day 3
AUCextra% was defined as area under the curve from time tlast extrapolated to infinity as percentage of AUC 0-infinity. Here, tlast is the last sampling time at which the concentration is at or above the lower limit of quantification.
Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; 48 hours post-dose on Day 3
Elimination Rate Constant (λz) of Metformin (GIR Tablet Active Ingredient)
Periodo de tiempo: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; 48 hours post-dose on Day 3
λz was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression method.
Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; 48 hours post-dose on Day 3
Total Body Clearance (CL/f) of Metformin (GIR Tablet Active Ingredient)
Periodo de tiempo: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; 48 hours post-dose on Day 3
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.
Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; 48 hours post-dose on Day 3
Apparent Volume of Distribution at After Extravascular Administration (Vz/f) of Metformin (GIR Tablet Active Ingredient)
Periodo de tiempo: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; 48 hours post-dose on Day 3
Vz/f is defined as the distribution of a study drug between plasma and the rest of the body after oral dosing.
Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; 48 hours post-dose on Day 3
Apparent Volume of Distribution at Steady-State After Extravascular Administration (Vss/f) of Metformin
Periodo de tiempo: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; 48 hours post-dose on Day 3
Vss/F was derived from concentration versus time data for all participants.
Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; 48 hours post-dose on Day 3
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs
Periodo de tiempo: Baseline up to Day 15
An Adverse event (AE) was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease associated with the use of study drug, whether or not considered related to the study drug or worsening of pre-existing medical condition, whether or not related to study drug. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. An AE was considered as 'treatment emergent' if it occurred after the first drug administration of each period or if it was present prior to drug administration but exacerbated after the drug administration. TEAEs included both Serious TEAEs and non-serious TEAEs.
Baseline up to Day 15
Number of Participants With Clinically Significant Abnormalities in Vital Signs, Laboratory Parameters, Physical Examination Findings and 12-lead Electrocardiogram (ECG) Findings
Periodo de tiempo: Baseline up to Day 15
The laboratory measurements included hematology, blood chemistry and urinalysis. Vital sign assessment included blood pressure, pulse rate and body temperature. ECG parameters included heart rate, PR, QRS,QT, RR, QTcB and QTcF Here, we are reporting number of participants with clinically significant abnormalities in Vital signs, laboratory parameters, physical findings and ECG findings.
Baseline up to Day 15

Colaboradores e Investigadores

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Publicaciones y enlaces útiles

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Fechas de registro del estudio

Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados ​​por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.

Fechas importantes del estudio

Inicio del estudio (Actual)

10 de enero de 2018

Finalización primaria (Actual)

29 de enero de 2018

Finalización del estudio (Actual)

29 de enero de 2018

Fechas de registro del estudio

Enviado por primera vez

22 de diciembre de 2017

Primero enviado que cumplió con los criterios de control de calidad

5 de enero de 2018

Publicado por primera vez (Actual)

8 de enero de 2018

Actualizaciones de registros de estudio

Última actualización publicada (Actual)

15 de julio de 2019

Última actualización enviada que cumplió con los criterios de control de calidad

3 de mayo de 2019

Última verificación

1 de abril de 2019

Más información

Términos relacionados con este estudio

Otros números de identificación del estudio

  • MS200084_0009

Información sobre medicamentos y dispositivos, documentos del estudio

Estudia un producto farmacéutico regulado por la FDA de EE. UU.

No

Estudia un producto de dispositivo regulado por la FDA de EE. UU.

No

Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .

Ensayos clínicos sobre Test GIR

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