diabetes mellitus HCV Hepatitis C
Conditions
Interventions
See study design:
Treatment A:
500mg BID metformin (day 1-2) increasing to 1,000mg BID metformin (day 3-8).
Day 8: 2h OGTT + PK-sampling metformin + glucose/insulin/lactate
Day 9-21: wash-out
Treat
Sponsors
Apotheek
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: Subjects must meet all of the following inclusion criteria to be eligible for participation in this study 1. Subject is at least 18 and not older than 55 years at screening. 2. Subject does not smoke more than 10 cigarettes, 2 cigars, or 2 pipes per day for at least 3 months prior to Day 1. 3. Subject has a Quetelet Index (Body Mass Index) of 18 to 35 kg/m2, extremes included. 4. Subject is able and willing to sign the Informed Consent Form prior to screening evaluations. 5. Subject is in good age-appropriate health condition as established by medical history, physical examination, and electrocardiography, results of biochemistry, haematology and urinalysis testing within 4 weeks prior to Day 1. Results of biochemistry, haematology and urinalysis testing should be within the laboratory's reference ranges (see Appendix A). If laboratory results are not within the reference ranges, the subject is included on condition that the Investigator judges that the deviations are not clinically relevant. This should be clearly recorded. 6. Subject has a normal blood pressure and pulse rate, according to the Investigator's judgement.
Exclusion criteria
Exclusion criteria: A potential subject who meets any of the following criteria will be excluded from partici-pation in this study: 1. Creatinine clearance below 60mL/min. 2. Documented history of sensitivity/idiosyncrasy to medicinal products or excipients. 3. Positive HIV test. 4. Positive hepatitis B or C test. 5. Pregnant female (as confirmed by an hCG test performed less than 4 weeks before day 1) or breastfeeding female. Female subjects of childbearing potential without adequate contraception, e.g. hysterectomy, bilateral tubal ligation, (non-hormonal) intrauterine device, total abstinence, double barrier methods, or two years post-menopausal. They must agree to take precautions in order to prevent a pregnancy throughout the entire conduct of the study. 6. Therapy with any drug (for two weeks preceding Day 1), except for acetaminophen (max 2 gram/day). 7. Relevant history or presence of pulmonary disorders (especially COPD), cardiovascular disorders, neurological disorders (especially seizures and migraine), psychiatric disorders, gastro-intestinal disorders, renal and hepatic disorders (increased ALAT/ASAT), hormonal disorders (especially diabetes mellitus), coagulation disorders. 8. Relevant history or current condition that might interfere with drug absorption, distribution, metabolism or excretion. 9. History of or current abuse of drugs, alcohol or solvents. 10. Inability to understand the nature and extent of the study and the procedures required. 11. Participation in a drug study within 60 days prior to Day 1. 12. Donation of blood within 60 days prior to Day 1. 13. Febrile illness within 3 days before Day 1.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To assess the effect of multiple dose daclatasvir (60mg QD) on the pharmacokinetics (AUC, Cmax, Ctrough, CLr) of multiple dose metformin (1,000mg BID) by intra-subject com-parison, in healthy subjects. The endpoints are geometric mean ratios of metformin AUC, Cmax, Ctrough with and without daclatasvir co-treatment. | — |
Secondary
| Measure | Time frame |
|---|---|
| The aim is to assess the effect of multiple dose daclatasvir (60mg QD) on the pharmaco-dynamics (OGTT) of multiple dose metformin (1,000mg BID) by intra-subject comparison, in healthy subjects. Secondary, to assess the steady-state pharmacokinetics of daclatasvir 60mg QD when given with metformin vs. historical controls and to evaluate the safety and tolerability of co administration of multiple doses of daclatasvir with or metformin, in healthy subjects. Geometric means of daclatasvir AUC, Cmax, and Ctrough compared to historical data and adverse effects will be evaluated. The endpoints are the OGTT results (glucose, insulin, and lactate) compared with and without daclatasvir co-treatment. Secondly, to assess the ex vivo, inflammatory response of monocytes, to study the in-fluence on metformin on monocytes. Finally, OCT-2 will be measured which will be use to describe the influence of different polymorphisms on possible metformin PK differences | — |
Countries
Netherlands
Outcome results
None listed