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

NCT03310749 | Completed Phase 1

• 1 other identifier: LG/STDHL-DPCL009bis
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Diabetes Mellitus, Type 2

Keywords

Type 2 Diabetes Mellitus; DPP-IV inhibitor; Drug-Drug Interactions; Ethnicity

Outcome Measures

Primary Outcomes (1)

• Gemigliptin AUCτ,ss Geometric Mean Ratio (and 90%CI)

  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 Outcomes (9)

• Gemigliptin Cmax,ss Geometric Mean Ratio (and 90%CI)

  At steady state, on the sixth planned treatment day

• Metformin AUCτ,ss Geometric Mean Ratio (and 90%CI)

  At steady state, on the sixth planned treatment day

• Metformin Cmax,ss Geometric Mean Ratio (and 90%CI)

  At steady state, on the sixth planned treatment day

• Ctrough,ss

  At steady state, on the sixth planned treatment day

• Aeτ,ss

  At steady state, on the sixth planned treatment day

Other Outcomes (1)

• Incidence of treatment-emergent adverse events

  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

Study Arms (3)

Treatment sequence A

OTHER

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.

Drug: Gemigliptin; Drug: Gemigliptin 50 mg q.d. + metformin 1000 mg twice a day; Drug: Metformin

Treatment sequence B

OTHER

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

Drug: Gemigliptin; Drug: Gemigliptin 50 mg q.d. + metformin 1000 mg twice a day; Drug: Metformin

Treatment sequence C

OTHER

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

Drug: Gemigliptin; Drug: Gemigliptin 50 mg q.d. + metformin 1000 mg twice a day; Drug: Metformin

Interventions

Gemigliptin DRUG

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

Also known as: Metformin, Gemigliptin 50 mg q.d. + metformin 1000 mg twice a day

Treatment sequence A; Treatment sequence B; Treatment sequence C

Gemigliptin 50 mg q.d. + metformin 1000 mg twice a day DRUG

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

Also known as: Gemigliptin, Metformin

Treatment sequence A; Treatment sequence B; Treatment sequence C

Metformin DRUG

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.

Also known as: Gemigliptin 50 mg q.d. + metformin 1000 mg twice a day, Gemigliptin

Treatment sequence A; Treatment sequence B; Treatment sequence C

Eligibility Criteria

• Age: 20 Years - 45 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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)
• \) Subjects who have had grapefruit/ any food containing caffeine within 3 days before the date of the first drug administration

Sponsors & Collaborators

• Stendhal Americas, S.A.: lead
• Universidad Nacional Autonoma de Mexico: collaborator
• LG Chem: collaborator

Study Sites (1)

Unidad de Farmacología Clínica de la Facultad de Medicina de la Universidad Nacional Autónoma de México

Nezahualcóyotl, State of Mexico, 57740, Mexico

Location

Related Publications (9)

• Kim SH, Jung E, Yoon MK, Kwon OH, Hwang DM, Kim DW, Kim J, Lee SM, Yim HJ. Pharmacological profiles of gemigliptin (LC15-0444), a novel dipeptidyl peptidase-4 inhibitor, in vitro and in vivo. Eur J Pharmacol. 2016 Oct 5;788:54-64. doi: 10.1016/j.ejphar.2016.06.016. Epub 2016 Jun 11.

  PMID: 27298192 BACKGROUND

• Lim KS, Kim JR, Choi YJ, Shin KH, Kim KP, Hong JH, Cho JY, Shin HS, Yu KS, Shin SG, Kwon OH, Hwang DM, Kim JA, Jang IJ. Pharmacokinetics, pharmacodynamics, and tolerability of the dipeptidyl peptidase IV inhibitor LC15-0444 in healthy Korean men: a dose-block-randomized, double-blind, placebo-controlled, ascending single-dose, Phase I study. Clin Ther. 2008 Oct;30(10):1817-30. doi: 10.1016/j.clinthera.2008.10.013.

  PMID: 19014837 BACKGROUND

• Lim KS, Cho JY, Kim BH, Kim JR, Kim HS, Kim DK, Kim SH, Yim HJ, Lee SH, Shin SG, Jang IJ, Yu KS. Pharmacokinetics and pharmacodynamics of LC15-0444, a novel dipeptidyl peptidase IV inhibitor, after multiple dosing in healthy volunteers. Br J Clin Pharmacol. 2009 Dec;68(6):883-90. doi: 10.1111/j.1365-2125.2009.03376.x.

  PMID: 20002082 BACKGROUND

• Kim N, Patrick L, Mair S, Stevens L, Ford G, Birks V, Lee SH. Absorption, metabolism and excretion of [14C]gemigliptin, a novel dipeptidyl peptidase 4 inhibitor, in humans. Xenobiotica. 2014 Jun;44(6):522-30. doi: 10.3109/00498254.2013.865856. Epub 2013 Dec 4.

  PMID: 24304170 BACKGROUND

• Ingelman-Sundberg M, Sim SC, Gomez A, Rodriguez-Antona C. Influence of cytochrome P450 polymorphisms on drug therapies: pharmacogenetic, pharmacoepigenetic and clinical aspects. Pharmacol Ther. 2007 Dec;116(3):496-526. doi: 10.1016/j.pharmthera.2007.09.004. Epub 2007 Oct 9.

  PMID: 18001838 BACKGROUND

• Zanger UM, Schwab M. Cytochrome P450 enzymes in drug metabolism: regulation of gene expression, enzyme activities, and impact of genetic variation. Pharmacol Ther. 2013 Apr;138(1):103-41. doi: 10.1016/j.pharmthera.2012.12.007. Epub 2013 Jan 16.

  PMID: 23333322 BACKGROUND

• Reyes-Hernandez OD, Lares-Asseff I, Sosa-Macias M, Vega L, Albores A, Elizondo G. A comparative study of CYP3A4 polymorphisms in Mexican Amerindian and Mestizo populations. Pharmacology. 2008;81(2):97-103. doi: 10.1159/000109983. Epub 2007 Oct 19.

  PMID: 17952011 BACKGROUND

• Shin D, Cho YM, Lee S, Lim KS, Kim JA, Ahn JY, Cho JY, Lee H, Jang IJ, Yu KS. Pharmacokinetic and pharmacodynamic interaction between gemigliptin and metformin in healthy subjects. Clin Drug Investig. 2014 Jun;34(6):383-93. doi: 10.1007/s40261-014-0184-3.

  PMID: 24627290 BACKGROUND

• Conde-Carmona I, Garcia-Medina S, Jimenez-Vargas JM, Martinez-Munoz A, Lee SH. Pharmacokinetic Interactions Between Gemigliptin and Metformin, and Potential Differences in the Pharmacokinetic Profile of Gemigliptin Between the Mexican and Korean Populations: A Randomized, Open-label Study in Healthy Mexican Volunteers. Clin Ther. 2018 Oct;40(10):1729-1740. doi: 10.1016/j.clinthera.2018.08.015. Epub 2018 Sep 22.

  PMID: 30249366 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

LC15-0444; Metformin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• Ignacio Conde-Carmona, MD

  Específicos Stendhal S.A. de C.V.

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Open, randomized, multiple dose, three way, three period, cross over, drug-drug interaction, safety and tolerability study

Study Record Dates

• First Submitted: September 13, 2017
• First Posted: October 16, 2017
• Study Start: January 15, 2016
• Primary Completion: May 3, 2016
• Study Completion: May 3, 2016
• Last Updated: October 16, 2017

Record last verified: 2017-10

Data Sharing

• IPD Sharing: Will not share

Locations

ME (1)