HealthyPhase 1NCT03583385

Glucophage® Extended Release (XR) 750 Milligram (mg) Indonesia Bioequivalence (BE) Study

A Phase 1 study testing Glucophage XR (Test drug) and Glucophage XR (Comparator drug) in people with Healthy, run by Merck KGaA, Darmstadt, Germany at 1 site in Indonesia.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

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. Read more about this study

Who is it for?: Ages 18 to 55 yearsHealthy volunteers can take part
Conditions the study is for: Healthy
What is being tested?: Glucophage XR (Test drug) and Glucophage XR (Comparator drug)
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 48 participants
Where: 1 siteIndonesia
Study dates: 16 Aug 2018to 5 Oct 2018
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 55 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

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)

Show all 11Show fewer

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.

Who cannot join

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)

Show all 12Show fewer

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)

Trial locations and contacts

1 site in 1 country.

Indonesia1 site

PT Equilab International
Jakarta, 12430

Other trials in Indonesia

About this study

Official title: 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

Conditions: Healthy
Being tested: Glucophage XR (Test drug), Glucophage XR (Comparator drug)

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Glucophage XR (Test drug)Drug
Also called Metformin hydrochloride
Participants received single oral dose of Glucophage® XR tablet manufactured by PT Merck Tbk, Jakarta, Indonesia (Test Drug) under fasted conditions.
Glucophage XR (Comparator drug)Drug
Also called Metformin hydrochloride
Participants received single oral dose of Glucophage® XR tablet manufactured by Merck Santé, Semoy, France (Comparator Drug) under fasted conditions.

Study groups in NCT03583385
Study group	Role	What they receive
First Glucophage XR (Test), Then Glucophage XR (Comparator)	Experimental	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. Receives: Drug: Glucophage XR (Test drug); Drug: Glucophage XR (Comparator drug)
First Glucophage XR (Comparator), Then Glucophage XR (Test)	Experimental	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. Receives: Drug: Glucophage XR (Test drug); Drug: Glucophage XR (Comparator drug)

What is being measured

The primary outcome is the main question the study is designed to answer.

Maximum Observed Plasma Concentration (Cmax) of Metformin
The maximum plasma concentration of Metformin.
Measured: 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
Area under the plasma concentration-time curve from zero to the time of the last quantifiable concentration.
Measured: 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 outcomes (4)

Area Under Plasma Concentration Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Metformin
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).
Measured: 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 of the maximum drug concentration.
Measured: 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
Terminal Elimination Half-life in Plasma (t½) of Metformin
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.
Measured: 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
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.
Measured: Up to Day 51

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

16 Aug 20185 Oct 2018

First posted11 Jul 2018
Study start16 Aug 2018
Primary completion5 Oct 2018
Study completion5 Oct 2018

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for HealthyStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Other
Allocation: Randomised
Intervention model: Crossover
Masking: Single blind
Who is masked: Outcomes assessor
Enrolment: 48 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03583385
Sponsor's protocol ID: MS200084_0015
Status last verified: Nov 2019
First submitted: 28 Jun 2018
Last updated: 25 Nov 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 25 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: 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
ClinicalTrials.gov ID: NCT03583385
Acronym / sponsor ID: MS200084_0015
Conditions: Healthy
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 48 participants (actual)
Lead sponsor: Merck KGaA, Darmstadt, GermanyIndustry (pharma, biotech, devices)
Study start: 16 Aug 2018 (actual)
Primary completion: 5 Oct 2018 (actual)
Study completion: 5 Oct 2018 (actual)
First posted: 11 Jul 2018 (actual)
Results: Posted 25 Nov 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Other
Allocation: Randomised
Intervention model: Crossover
Masking: Single blind (outcomes assessor)
Number of arms: 2

Arm	Type	Receives
First Glucophage XR (Test), Then Glucophage XR (Comparator)	Experimental	Drug: Glucophage XR (Test drug), Drug: Glucophage XR (Comparator drug)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.
First Glucophage XR (Comparator), Then Glucophage XR (Test)	Experimental	Drug: Glucophage XR (Test drug), Drug: Glucophage XR (Comparator drug)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.

Who may qualify

Ages: 18 to 55 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (11 listed)

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

Key exclusion criteria (12 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Glucophage XR (Test drug)Also: Metformin hydrochlorideParticipants received single oral dose of Glucophage® XR tablet manufactured by PT Merck Tbk, Jakarta, Indonesia (Test Drug) under fasted conditions.	Drug	First Glucophage XR (Comparator), Then Glucophage XR (Test), First Glucophage XR (Test), Then Glucophage XR (Comparator)
Glucophage XR (Comparator drug)Also: Metformin hydrochlorideParticipants received single oral dose of Glucophage® XR tablet manufactured by Merck Santé, Semoy, France (Comparator Drug) under fasted conditions.	Drug	First Glucophage XR (Comparator), Then Glucophage XR (Test), First Glucophage XR (Test), Then Glucophage XR (Comparator)

Primary outcome

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.
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
Area under the plasma concentration-time curve from zero to the time of the last quantifiable concentration.

4 secondary outcomes

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
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
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
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs
Time frame: Up to Day 51

Results and safety

Results posted to the registry on 25 Nov 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
First Glucophage XR (Test), Then Glucophage XR (Comparator)	24	23
First Glucophage XR (Comparator), Then Glucophage XR (Test)	24	23

Primary outcome: 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. Mean (Standard Deviation). Unit: Nano-gram per milliliter (ng/mL)

Measure	Glucophage XR (Test) n = 43	Glucophage XR (Comparator) n = 43
Value	1109 (318.4)	1087 (336.3)

Glucophage XR (Test) vs Glucophage XR (Comparator): % Ratio of Geometric Means: 103.42 (90% CI 95.18 to 112.37)

Population analysed: Pharmacokinetic (PK) analysis set included all participants without any relevant protocol deviations with respect to PK and absence of factors likely to affect the comparability of PK results, with adequate study medication compliance, and who have valid primary endpoints for both treatment.

Primary outcome: 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. Mean (Standard Deviation). Unit: Nanogram*hour per milliliter (ng*h/mL)

Measure	Glucophage XR (Test) n = 43	Glucophage XR (Comparator) n = 43
Value	7387 (2535.7)	6977 (2512.0)

Glucophage XR (Test) vs Glucophage XR (Comparator): % Ratio of Geometric Means: 106.78 (90% CI 98.99 to 115.19)

Population analysed: PK analysis set included all participants without any relevant protocol deviations with respect to PK and absence of factors likely to affect the comparability of PK results, with adequate study medication compliance, and who have valid primary endpoints for both treatment.

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: Up to Day 51. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Glucophage XR (Test)	0 of 47 (0%)	5 of 47 (10.6%)	0 of 47
Glucophage XR (Comparator)	0 of 46 (0%)	9 of 46 (19.6%)	0 of 46

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 25 Nov 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Medical Responsible study director

PT Merck Tbk, Indonesia, and affiliate of Merck KGaA, Darmstadt, Germany

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Glucophage XR (Test drug) and Glucophage XR (Comparator drug) in people with Healthy, run by Merck KGaA, Darmstadt, Germany at 1 site in Indonesia.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 25 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Indonesia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 25 Nov 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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 study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03583385.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Nov 2019; AzTrials last refreshed its copy on 8 Nov 2026.