A Drug Interaction Study of VI-0521 With Metformin, Sitagliptan and Probenecid in Healthy Subjects.
Condition: Obesity
MeSH terms: Obesity
Study type: Interventional
Phase: Phase 1

Summary: 
      The purposes of this study are to:

        -  Find out how much of the study drugs are in the blood of healthy subjects after taking
           multiple doses of VI-0521, metformin and sitagliptan.

        -  Determine the effect of probenecid on the amount of VI-0521 in the blood of healthy
           subjects after taking multiple doses.

        -  Find out how much topiramate is in the semen of healthy male subjects after taking
           multiple doses.
    

Detailed description: 
      This trial is an open-label, non-randomized, one-sequence crossover study. All subjects will
      receive an oral dose of metformin 500 mg tablet twice daily on Days 1 to 5 and on Days 30 to
      34; an oral dose of sitagliptin 100 mg tablet once daily on Days 6 to 10 and on Days 35 to 39
      and a single oral dose of VI-0521 (phentermine/topiramate) capsule once daily each morning at
      3.75/23 mg for 2 days (Days 11-12), 7.5/46 mg for 3 days (Days 13-15), 11.25/69 mg for 3 days
      (Days 16-18) and 15/92 mg for 21 days (Days 19-39) plus a single oral dose of 2 g (four 500
      mg) probenecid tablets on Day 29.

      Subjects will remain at the site for the duration of the study (from Day -1 to Day 40). Blood
      samples for the determination of metformin concentrations in plasma will be collected at 0
      (pre-dose), 1, 2, 3, 4, 6, 8 and 12 hours after the morning administration of metformin or
      metformin plus VI-0521 on Days 5 and 34. Blood samples for the determination of sitagliptin
      concentrations in plasma will be collected at 0 (pre-dose), 1, 2, 3, 4, 5, 7, 10, 16 and 24
      hours after the administration of sitagliptin or sitagliptin plus VI-0521 on Days 10 and 39.
      Blood samples for the determination of phentermine and topiramate concentrations in plasma
      will be collected at 0 (pre-dose), 1, 2, 3, 4, 5, 7, 10, 16 and 24 hours after the
      administration of the investigational product(s) on Days 28, 29, 34 and 39. Pre-dose blood
      samples for determination of the investigational drug concentrations in plasma will be taken
      in the morning on Days 4 and 33 for metformin; Days 9 and 38 for sitagliptin and Days 27, 33
      and 38 for phentermine and topiramate. Semen samples for determination of topiramate
      concentrations will be collected on Day 28 between five and seven hours after VI-0521
      administration in 8 male non-vasectomized subjects to obtain at least 6 evaluable subjects.

      The primary endpoints of this study will be the PK parameters AUC0-τ and Cmax of phentermine,
      topiramate, sitagliptin and metformin.The secondary endpoint is the topiramate concentration
      in semen.
    

Intervention name(s): Metformin, VI-0521, Sitagliptan, Probenecid
Intervention type(s): Drug
Intervention description(s): This trial is an open-label, non-randomized, one-sequence crossover study.
metformin 500 mg tablet twice daily on Days 1 to 5 and on Days 30 to 34
sitagliptan 100 mg tablet once daily on Days 6 to 10 and on Days 35 to 39
VI-0521 (phentermine/topiramate) capsule once daily each morning at 3.75/23 mg for 2 days (Days 11-12), 7.5/46 mg for 3 days (Days 13-15), 11.25/69 mg for 3 days (Days 16-18) and 15/92 mg for 21 days (Days 19-39)
2 g (four 500 mg) probenecid tablets on Day 29.
Other intervention name(s): VI-0521, Sitagliptan, Metformin, Probenecid
Intervention MeSH terms: Metformin; Probenecid
Allocation: Non-Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Keywords: Obesity