Effect of Co-administration of Metformin and Daclatasvir on the Pharmacokinetis and Pharmacodynamics of Metformin
Condition: Diabetes Mellitus, Type 2; Hepatitis C; Drug Interactions
MeSH terms: Hepatitis C; Diabetes Mellitus, Type 2
Study type: Interventional
Phase: Phase 1

Summary: 
      A Randomized,Two-period, Crossover Study to Determine the Possibility of Drug-drug
      Interaction After Co-administration of Metformin and Daclatasvir Where Twenty Eligible Adult
      Subjects Will be Randomized to Receive Either Metformin Only and/or Metformin Co-administered
      With Daclatasvir to measure primary outcomes including pharmacokinetics parameters as:
      Maximum drug concentration in plasma(Cmax), Area under the Plasma concentration Versus Time
      Curve from time 0 to 12 hours(AUC0-12), Clearance(CL)
    

Detailed description: 
      Study Design:

      A randomized, one-way, single blinded, two-period, crossover study in adult human healthy
      egyptian volunteers

      Methodology:

      period (I): Group A:10 volunteers will receive 500 mg Metformin twice daily on day 1-4 then
      1000mg metformin twice on day 5-7

      GroupB:10 volunteers will receive 500 mg Metformin twice daily + Daclatasvir (DCV) 60 mg once
      daily on day 1-4 then 1000mg metformin twice daily+DCV 60 mg once daily on day 5-7

      period (II): Group A:10 volunteers will receive 500 mg Metformin twice daily + Daclatasvir
      (DCV) 60 mg once daily on day 1-4 then 1000mg metformin twice daily+DCV 60 mg once daily on
      day 5-7

      Group B:10 volunteers will receive 500 mg Metformin twice daily on day 1-4 then 1000mg
      metformin twice daily on day 5-7

      All drug administration will be followed by 240 ml of water after at least 10 hours fasting
      prior to administration.

      The two treatment periods will be separated by a one week washout period

      Blood Sampling will be collected at a pre-dosing and at 0.25, 0.33, 0.5, 0.75, 1, 1.5, 2,
      2.5, 3, 3.5, 4, 6, 8, 10, 12 hours Urine samples will be collected for metformin analysis
      from 0 to 12 hours after drug administration.

      A 75 g Oral glucose tolerance test(OGTT) will be carried out by ingestion of 75g glucose in
      240ml water 2-hours post dosing and blood samples for determining glucose concentration
      during OGTTs were collected immediately before and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, and 3
      hours after glucose ingestion.

      Blood samples will be collected from each volunteer prior to drug administration (blank) at
      the predetermined sampling intervals after drug administration in ethylene diamine
      tetra-acetic acid(kEDTA) containing tubes.

      These samples will be centrifuged and the plasma harvested and stored at -80°C until assay.
    

Intervention name(s): Metformin; Daclatasvir
Intervention type(s): Drug; Drug
Intervention description(s): Metformin is used primarly in treatment of diabetes type II; Daclatsvir is a direct acting antiviral drug
Intervention MeSH terms: Metformin
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: Twenty Eligible Adult Subjects Will be Randomized Equally into two Groups: A and B To Receive Either:
Group (A):10 subjects will receive 500 mg Metformin twice daily on day 1-4 then 1000mg metformin twice on day 5-7 Group (B):10 subjects will receive 500 mg co-administered daily with Daclatasvir 60 mg once daily on day 1-4 then 1000mg Metformin co-administered twice daily with Daclatasvir 60 mg once daily on day 5-7
Masking: Double (Investigator, Outcomes Assessor)
Primary purpose: Other