An Assessment of Pharmacokinetic Gemigliptin and Metformin Interactions in Healthy Mexican Volunteers
Condition: Diabetes Mellitus, Type 2
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Study type: Interventional
Phase: Phase 1

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.
    

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.
    

Intervention name(s): Gemigliptin; Gemigliptin 50 mg q.d. + metformin 1000 mg twice a day; Metformin
Intervention type(s): Drug; Drug; Drug
Intervention description(s): 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; 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; 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 intervention name(s): Metformin; Gemigliptin 50 mg q.d. + metformin 1000 mg twice a day; Gemigliptin; Metformin; Gemigliptin 50 mg q.d. + metformin 1000 mg twice a day; Gemigliptin
Intervention MeSH terms: Metformin
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: Open, randomized, multiple dose, three way, three period, cross over, drug-drug interaction, safety and tolerability study
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Type 2 Diabetes Mellitus; DPP-IV inhibitor; Drug-Drug Interactions; Ethnicity