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.
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
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
34
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.
Unidad de Farmacología Clínica de la Facultad de Medicina de la Universidad Nacional Autónoma de México
Nezahualcóyotl, State of Mexico, Mexico
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)
Time frame: At steady state, on the sixth planned treatment day
Gemigliptin Cmax,ss Geometric Mean Ratio (and 90%CI)
Cmax,ss Geometric Mean Ratio for gemigliptin when administered concomitanty with metformin (test) to its administration alone (reference)
Time frame: At steady state, on the sixth planned treatment day
Metformin AUCτ,ss Geometric Mean Ratio (and 90%CI)
AUCτ,ss Geometric Mean Ratio for metformin when administered concomitanty with metformin (test) to its administration alone (reference)
Time frame: At steady state, on the sixth planned treatment day
Metformin Cmax,ss Geometric Mean Ratio (and 90%CI)
Cmax,ss Geometric Mean Ratio for metformin when administered concomitanty with metformin (test) to its administration alone (reference)
Time frame: At steady state, on the sixth planned treatment day
Ctrough,ss
Lowest plasma concentration prior to the next dose administration at steady state
Time frame: At steady state, on the sixth planned treatment day
Aeτ,ss
cumulative amount of drug excreted in the urine during a dosing interval
Time frame: At steady state, on the sixth planned treatment day
CLss/F
Apparent drug clearance
Time frame: At steady state, on the sixth planned treatment day
CLR,ss
Renal drug clearance
Time frame: At steady state, on the sixth planned treatment day
MR
Metabolic ratio
Time frame: At steady state, on the sixth planned treatment day
Tmax
Time to maximum plasma concentration at steady state
Time frame: At steady state, on the sixth planned treatment day
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.