An Assessment of Pharmacokinetic Gemigliptin and Metformin Interactions in Healthy Mexican Volunteers

October 13, 2017 updated by: Stendhal Americas, S.A.

A Randomized, Open-label, Multiple Dosing, Three-way Crossover Clinical Trial to Investigate the Pharmacokinetic Drug-drug Interaction of Gemigliptin and Metformin After Oral Administration in Healthy Mexican Male Subjects

This is an open, randomized (randomization ratio: 1:1), multiple dose, three way, three period cross over study to assess the potential for drug drug interactions between gemigliptin (a DPP-IV inhibitor mainly metabolized by CYP3A4) and metformin in a sample of healthy Mexican volunteers, aimed to determine whether the observed lack of drug-drug interactions between gemigliptin and metformin in the Korean population is reproducible in an ethnically different population characterized by a significant difference in the frequency of CYP3A4 polymorphisms associated with decreased enzymatic activity, such as CYP3A4*1b, in comparison with Asian populations.

Study Overview

Detailed Description

Consenting, eligible healthy adult subjects sequentially received either gemigliptin 50 mg q.d., metformin 1000 mg twice a day or gemigliptin 50 mg q.d. plus metformin 1000 mg twice a day during 3 consecutive 7 day treatment periods separated by two 5-day washout intervals, in accordance with a randomly assigned treatment sequence. Starting on the sixth treatment period day, participating subjects underwent safety assessments and repeated (24 hour) blood and urine sampling for pharmacokinetic analysis. All subjects attended to a post-study visit for final safety assessments within 8 days of study completion or early withdrawal.

Urine and plasma samples where processed to determine gemigliptin and metformin concentrations using validated analytical methods and pharmacokinetic profiles of both gemigliptin and metformin were obtained using a non-compartmental method; both the rate and degree of gemigliptin and metformin absorption resulting from their concomitant administration relative to the administration of each drug alone were assessed in search of potential pharmacokinetic interactions, Finally, a post hoc assessment of the degree and rate of the absorption of gemigliptin in the study population relative to those of a group of Korean subjects participating in phase I, repeated dose gemigliptin studies was conducted.

Study Type

Interventional

Enrollment (Actual)

34

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

    • Estado de México
      • Nezahualcóyotl, Estado de México, Mexico, 57740
        • Unidad de Farmacología Clínica de la Facultad de Medicina de la Universidad Nacional Autónoma de México

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

20 years to 45 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

Inclusion Criteria:

  • Healthy male subjects at age between 20 and 45 at the screening test
  • Subjects with a body weight of 55kg or more but less than 90kg and a Body Mass Index (BMI) of between 18.0 or more but less than 27.0

    • BMI (kg/m2) = Weight (kg) / {Height (m)}2
  • Subjects who show the blood glucose level within the range of 70-125 mg/dL at the fasting plasma glucose (FPG) test conducted at screening
  • Subjects who fully understand this clinical trial after hearing a detailed explanation about it, make a decision to participate in it by his/her own free will, and sign an informed consent form to comply with the precautions

Exclusion Criteria:

  • Subjects who have a present condition or past history of any disease involving liver, kidney, nervous system, immune system, respiratory system, or endocrine system, hematologic and oncologic disease, cardiovascular disease, or psychiatric disorder (mood disorder, obsessive-compulsive disorder, etc.) (including subjects carrying hepatitis virus in case of liver disease)
  • Subjects with a past history of a gastrointestinal system disease (Crohn's disease, ulcer, acute or chronic pancreatitis, etc.) or a gastrointestinal system surgery (however, subjects with a history of appendectomy or hernioplasty are not excluded)
  • Subjects with a medical history of allergic reaction to drugs (aspirin, antibiotics, etc.) or clinically significant hypersensitivity reaction
  • Subjects who show one of the following results at screening test:

    • Exceeds 1.5 times the upper limit of the normal range of blood AST (SGOT) and ALT (SGPT)
    • The creatinine clearance calculated by Cockcroft-Gault equation is below 80 mL/min.
    • QTc > 450 ms in ECG or clinically significant abnormal rhythm
  • In the vital signs measured in sitting position after a rest for 3 minutes or longer, subjects who showed a systolic blood pressure of ≤ 100 mmHg or ≥ 150 mmHg, or a diastolic blood pressure of ≤ 60 mmHg or ≥ 95 mmHg)
  • Subjects who have a past history of drug abuse or have shown a positive reaction to drugs that are used in abusive manner or cotinine at a urine drug screening
  • Subjects who have taken any ethical drug or an herbal medication within 2 weeks before the date of first administration or have taken any over-the-counter (OTC) drug or vitamin preparation within 1 week (however, they can be included as subjects if considered appropriate at the investigator's discretion judgment)
  • Subject who have already participated in other clinical trials within 2 months before the date of first drug administration
  • Subject who have had whole blood donation within 2 months or component blood donation within 1 month before the date of first drug administration, or transfusion in 1 month before the date of first drug administration
  • Subjects who have been drinking alcohol continuously (more than 21 units/week, 1 unit = 10 g of pure alcohol) or can't refrain from drinking alcohol during the clinical trial period
  • Smokers (however, if the subject stopped smoking more than 3 months before the date of the first drug administration, he/she can be selected as a subject)
  • 12) Subjects who have had grapefruit/ any food containing caffeine within 3 days before the date of the first drug administration

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: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: Treatment sequence A
Gemigliptin 50 mg q.d. during 7 days, metformin 1000 mg twice a day during 7 days and gemigliptin 50 mg q.d + metformin 1000 mg twice a day during 7 days.
A 7-day treatment period with gemigliptin 50 mg q.d., followed by a 5-day washout period; a 7 day treatment period with metformin 1000 mg twice a day followed by a 5-day washout period and a final 7-day treatment period with gemigliptin 50 mg q.d. + metformin 1000 mg twice a day
Other Names:
  • Metformin
  • Gemigliptin 50 mg q.d. + metformin 1000 mg twice a day
A 7-day treatment period with gemigliptin 50 mg q.d. + metformin 1000 mg twice a day followed by a 5-day washout period; a 7-day treatment period with gemigliptin 50 mg q.d. followed by a 5-day washout period and a final 7-day treatment period with metformin 1000 mg twice a day
Other Names:
  • Metformin
  • Gemigliptin
A 7-day treatment period with 1000 mg metformin twice a day followed by a 5-day washout period; a 7-day treatment period with gemigliptin 50 mg q.d.+ metformin 1000 mg twice a day followed by a 5-day washout period and a final 7-day treatment period with gemigliptin 50 mg q.d.
Other Names:
  • Gemigliptin 50 mg q.d. + metformin 1000 mg twice a day
  • Gemigliptin
Other: Treatment sequence B
Gemigliptin 50 mg q.d + metformin 1000 mg twice a day during 7 days, gemigliptin 50 mg q.d. during 7 days, metformin 1000 mg twice a day during 7 days
A 7-day treatment period with gemigliptin 50 mg q.d., followed by a 5-day washout period; a 7 day treatment period with metformin 1000 mg twice a day followed by a 5-day washout period and a final 7-day treatment period with gemigliptin 50 mg q.d. + metformin 1000 mg twice a day
Other Names:
  • Metformin
  • Gemigliptin 50 mg q.d. + metformin 1000 mg twice a day
A 7-day treatment period with gemigliptin 50 mg q.d. + metformin 1000 mg twice a day followed by a 5-day washout period; a 7-day treatment period with gemigliptin 50 mg q.d. followed by a 5-day washout period and a final 7-day treatment period with metformin 1000 mg twice a day
Other Names:
  • Metformin
  • Gemigliptin
A 7-day treatment period with 1000 mg metformin twice a day followed by a 5-day washout period; a 7-day treatment period with gemigliptin 50 mg q.d.+ metformin 1000 mg twice a day followed by a 5-day washout period and a final 7-day treatment period with gemigliptin 50 mg q.d.
Other Names:
  • Gemigliptin 50 mg q.d. + metformin 1000 mg twice a day
  • Gemigliptin
Other: Treatment sequence C
Metformin 1000 mg twice a day during 7 days, gemigliptin 50 mg q.d + metformin 1000 mg twice a day during 7 days, gemigliptin 50 mg q.d. during 7 days
A 7-day treatment period with gemigliptin 50 mg q.d., followed by a 5-day washout period; a 7 day treatment period with metformin 1000 mg twice a day followed by a 5-day washout period and a final 7-day treatment period with gemigliptin 50 mg q.d. + metformin 1000 mg twice a day
Other Names:
  • Metformin
  • Gemigliptin 50 mg q.d. + metformin 1000 mg twice a day
A 7-day treatment period with gemigliptin 50 mg q.d. + metformin 1000 mg twice a day followed by a 5-day washout period; a 7-day treatment period with gemigliptin 50 mg q.d. followed by a 5-day washout period and a final 7-day treatment period with metformin 1000 mg twice a day
Other Names:
  • Metformin
  • Gemigliptin
A 7-day treatment period with 1000 mg metformin twice a day followed by a 5-day washout period; a 7-day treatment period with gemigliptin 50 mg q.d.+ metformin 1000 mg twice a day followed by a 5-day washout period and a final 7-day treatment period with gemigliptin 50 mg q.d.
Other Names:
  • Gemigliptin 50 mg q.d. + metformin 1000 mg twice a day
  • Gemigliptin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Gemigliptin AUCτ,ss Geometric Mean Ratio (and 90%CI)
Time Frame: At steady state, on the sixth planned treatment day
AUCτ,ss Geometric Mean Ratio for gemigliptin when administered concomitanty with metformin (test) to its administration alone (reference)
At steady state, on the sixth planned treatment day

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Gemigliptin Cmax,ss Geometric Mean Ratio (and 90%CI)
Time Frame: At steady state, on the sixth planned treatment day
Cmax,ss Geometric Mean Ratio for gemigliptin when administered concomitanty with metformin (test) to its administration alone (reference)
At steady state, on the sixth planned treatment day
Metformin AUCτ,ss Geometric Mean Ratio (and 90%CI)
Time Frame: At steady state, on the sixth planned treatment day
AUCτ,ss Geometric Mean Ratio for metformin when administered concomitanty with metformin (test) to its administration alone (reference)
At steady state, on the sixth planned treatment day
Metformin Cmax,ss Geometric Mean Ratio (and 90%CI)
Time Frame: At steady state, on the sixth planned treatment day
Cmax,ss Geometric Mean Ratio for metformin when administered concomitanty with metformin (test) to its administration alone (reference)
At steady state, on the sixth planned treatment day
Ctrough,ss
Time Frame: At steady state, on the sixth planned treatment day
Lowest plasma concentration prior to the next dose administration at steady state
At steady state, on the sixth planned treatment day
Aeτ,ss
Time Frame: At steady state, on the sixth planned treatment day
cumulative amount of drug excreted in the urine during a dosing interval
At steady state, on the sixth planned treatment day
CLss/F
Time Frame: At steady state, on the sixth planned treatment day
Apparent drug clearance
At steady state, on the sixth planned treatment day
CLR,ss
Time Frame: At steady state, on the sixth planned treatment day
Renal drug clearance
At steady state, on the sixth planned treatment day
MR
Time Frame: At steady state, on the sixth planned treatment day
Metabolic ratio
At steady state, on the sixth planned treatment day
Tmax
Time Frame: At steady state, on the sixth planned treatment day
Time to maximum plasma concentration at steady state
At steady state, on the sixth planned treatment day

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of treatment-emergent adverse events
Time Frame: From the first pre-treatment admission date, trough the 39 days required for completion of the planned treatment/sampling and washout periods up to and including the post-study safety visit, conducted at study day 44
Incidence of adverse events occuring during the exposure to the study medications
From the first pre-treatment admission date, trough the 39 days required for completion of the planned treatment/sampling and washout periods up to and including the post-study safety visit, conducted at study day 44

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Study Chair: Ignacio Conde-Carmona, MD, Específicos Stendhal S.A. de C.V.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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)

January 15, 2016

Primary Completion (Actual)

May 3, 2016

Study Completion (Actual)

May 3, 2016

Study Registration Dates

First Submitted

September 13, 2017

First Submitted That Met QC Criteria

October 13, 2017

First Posted (Actual)

October 16, 2017

Study Record Updates

Last Update Posted (Actual)

October 16, 2017

Last Update Submitted That Met QC Criteria

October 13, 2017

Last Verified

October 1, 2017

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

IPD Plan Description

No formal plan has been established since at the time the study was conducted no consent was obtained from the subjects to share their individual data for research purposes different from those specifically defined in the study protocol

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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