- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03583385
Glucophage® Extended Release (XR) 750 Milligram (mg) Indonesia Bioequivalence (BE) Study
November 5, 2019 updated by: Merck KGaA, Darmstadt, Germany
A Randomized, Open-label, Two-way Crossover Study Assessing the Bioequivalence (BE) Between Single Dose of 750 mg Glucophage® XR Tablets (PT Merck Tbk, Jakarta, Indonesia-Manufactured) and 750 mg Glucophage® XR Tablets (Merck Santé, Semoy, France-Manufactured) Under Fasted State in Healthy Subjects
The purpose of this study is to assess bioequivalence between metformin hydrochloride (Glucophage® XR) manufactured in PT Merck Tbk, Indonesia (test drug) and metformin hydrochloride (Glucophage® XR) manufactured in Merck Santé, France (comparator drug) following single oral dose administration under fasting condition.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
48
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
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Jakarta, Indonesia, 12430
- PT Equilab International
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-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 55 years (Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Participants has provided written informed consent prior to the conduct of any study-related activities
- Body mass index of 18 to 25 kilogram per square meter (kg/m^2)
- Good physical and mental health status, determined on the basis of medical history and physical examination
- Vital signs (blood pressure, pulse rate, respiratory rate and body temperature) in sitting position within the normal range or showing no clinically relevant deviation per the Investigator's opinion
- All values for laboratory assessments (hematology, clinical chemistry and urinalysis) within the normal range or showing no clinically relevant deviation per the Investigator's opinion
- No clinically significant abnormality on 12-lead electrocardiogram (ECG) recording as judged by the Investigator; corrected QT interval (QTc) (Bazett) should be less than equals to (<=) 450 milliseconds (ms)
- Non-smoker or smoker less than 10 cigarettes per day
- Women of childbearing potential (WOCBP) who are not nursing, are not pregnant, and are using highly effective methods of birth control. Female participants may also be enrolled if they are postmenopausal or surgically sterilized/ hysterectomized at least 6 months prior to study participation
- WOCBP must have a negative urine pregnancy test at Screening and on each admission (Day 1 of each dosing period)
- Negative screen for alcohol and drugs abuse (opiate class, barbiturates, cocaine and metabolites, amphetamines, cannabinoids and benzodiazepines) at Screening and on each Study Check-In (Day -1 of each dosing period)
- Negative screen for Hepatitis B surface antigen (HBsAg), Hepatitis C Virus (HCV) antibodies and/or Human Immunodeficiency Virus (HIV) antibodies.
Exclusion Criteria:
- Participation in a clinical trial/study within 90 days prior to Screening
- Blood donation (equal or more than 300 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 prestudy 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 study or that could interfere with the study objectives, conduct or evaluation
- History of malignant diseases, except in-situ basal cell skin tumors treated with curative intent
- History of surgery of the gastrointestinal tract which could influence the gastrointestinal absorption and/or motility per the Investigator's opinion
- History or presence of relevant liver diseases or hepatic dysfunction (laboratory result for liver function test greater than equals to (>=) 1.5 upper limit of normal (ULN)
- History or presence of renal failure or renal dysfunction based on clinical symptoms and finding (serum creatinine concentration >1.4 milligram per milliliter (mg/mL)
- 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 considers may affect the outcome of the study
- Receipt of any prescription or non-prescription medication within 14 days before the first drug administration, except for hormonal contraceptives in female, and including multivitamins and herbal products (e.g. St John's Wort)
- Consumption of large quantities of methylxanthine-containing beverages (> 5 cups of coffee/day or equivalent)
- Consumption of grapefruit, orange, cranberry or juices of these three fruits, 24 hours prior to drug administration
- Known lack of participant compliance or inability to communicate or cooperate with the Investigator (e.g., language problem, poor mental status)
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Other
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Single
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: First Glucophage XR (Test), Then Glucophage XR (Comparator)
Participants received single oral dose of 750 milligram (mg) Glucophage® XR tablet manufactured by PT Merck Tbk, Jakarta, Indonesia (Test Drug) in treatment period 1 followed by single oral dose of 750 mg Glucophage® XR tablet manufactured by Merck Santé, Semoy, France (Comparator Drug) in treatment period 2 under fasting conditions.
The two periods were separated by a 7-day wash-out period.
|
Participants received single oral dose of Glucophage® XR tablet manufactured by PT Merck Tbk, Jakarta, Indonesia (Test Drug) under fasted conditions.
Other Names:
Participants received single oral dose of Glucophage® XR tablet manufactured by Merck Santé, Semoy, France (Comparator Drug) under fasted conditions.
Other Names:
|
Experimental: First Glucophage XR (Comparator), Then Glucophage XR (Test)
Participants received single oral dose of 750 milligram (mg) Glucophage® XR tablet manufactured by Merck Santé, Semoy, France (Comparator Drug) in treatment period 1 followed by single oral dose of 750 mg Glucophage® XR tablet manufactured by PT Merck Tbk, Jakarta, Indonesia (Test Drug) in treatment period 2 under fasting conditions.
The two periods were separated by a 7-day wash-out period.
|
Participants received single oral dose of Glucophage® XR tablet manufactured by PT Merck Tbk, Jakarta, Indonesia (Test Drug) under fasted conditions.
Other Names:
Participants received single oral dose of Glucophage® XR tablet manufactured by Merck Santé, Semoy, France (Comparator Drug) under fasted conditions.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Maximum Observed Plasma Concentration (Cmax) of Metformin
Time Frame: Pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 10, 12, 16, 24, and 32 hours post-dose on Day 1
|
The maximum plasma concentration of Metformin.
|
Pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 10, 12, 16, 24, and 32 hours post-dose on Day 1
|
Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Metformin
Time Frame: Pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 10, 12, 16, 24, and 32 hours post-dose on Day 1
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Area under the plasma concentration-time curve from zero to the time of the last quantifiable concentration.
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Pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 10, 12, 16, 24, and 32 hours post-dose on Day 1
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Area Under Plasma Concentration Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Metformin
Time Frame: Pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 10, 12, 16, 24, and 32 hours post-dose on Day 1
|
AUC (0-inf) is defined as the area under the plasma concentration versus time curve (AUC) from time zero (predose) to extrapolated infinite time (0-inf).
|
Pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 10, 12, 16, 24, and 32 hours post-dose on Day 1
|
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Metformin
Time Frame: Pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 10, 12, 16, 24, and 32 hours post-dose on Day 1
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Time of the maximum drug concentration.
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Pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 10, 12, 16, 24, and 32 hours post-dose on Day 1
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Terminal Elimination Half-life in Plasma (t½) of Metformin
Time Frame: Pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 10, 12, 16, 24, and 32 hours post-dose on Day 1
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Elimination Half Life (t1/2) was defined as the time required for the concentration or amount of drug in the body to be reduced by one-half.
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Pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 10, 12, 16, 24, and 32 hours post-dose on Day 1
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs
Time Frame: Up to Day 51
|
An adverse event (AE) was defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with the treatment.
An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, whether or not considered related to the medicinal product.
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.
The term TEAE is defined as AEs starting or worsening after the first intake of the study drug.
Number of participants with TEAEs included participants with both non serious and serious TEAEs.
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Up to Day 51
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Study Director: Medical Responsible, PT Merck Tbk, Indonesia, and affiliate of Merck KGaA, Darmstadt, Germany
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
August 16, 2018
Primary Completion (Actual)
October 5, 2018
Study Completion (Actual)
October 5, 2018
Study Registration Dates
First Submitted
June 28, 2018
First Submitted That Met QC Criteria
June 28, 2018
First Posted (Actual)
July 11, 2018
Study Record Updates
Last Update Posted (Actual)
November 25, 2019
Last Update Submitted That Met QC Criteria
November 5, 2019
Last Verified
November 1, 2019
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- MS200084_0015
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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