None
Conditions
Sponsors
Furihata Kenichi
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: a)Healthy men at >=20 but <40 years of age when the consent was obtained. b)Body mass index (BMI) at screening is between 18.5 and 25.0, and body weight is 50 kg or more. c)Persons who were judged appropriate as subjects by the investigator (sub-investigator) based on medical history and physical exam and laboratory tests at screening. d)Agree to the following during the administration period and for 10 days after the last dose of study drug - Not to donate sperm. In addition - Do not engage in heterosexual sexual intercourse or - During intercourse with a woman of childbearing potential, in addition to the use of male condoms, the female partner must use a contraceptive method [oral hormonal contraceptive combination (estrogen-progestin combination), intrauterine hormone release system (IUS), intrauterine device without added hormones (IUD), bilateral tubal ligation]. consent to the use of bilateral tubal ligation]. e)Subjects who can understand and comply with the protocol and from whom the written consent based on his or her own free will can be obtained.
Exclusion criteria
Exclusion criteria: a)Persons with a history of hypersensitivity to metformin or biguanide drug, Cimetidine, Dolutegravir. b)Persons who are contraindicated for administration of metformin. Persons who are in the following state(Persons who are liable to cause lactic acidosis.) (1) history of lactic acidosis (2) renal dysfunction of moderate or higher (3) dialysis patients (including peritoneal dialysis) (4) severe liver dysfunction, (5) shock, heart failure, myocardial infarction (6) excessive alcohol intake (7) Patients with gastrointestinal disorders such as vomiting, dehydration or diarrhea in which dehydration are a concern. -Patients with severe ketosis, diabetic coma or precoma, type 1 diabetes (infusion, correction of rapid hyperglycemia by insulin is essential.) -Severe infection, patients before and after surgery, patients with severe trauma (Administration of this drug is not suitable because it is desired to control blood glucose by insulin injection. Also, it is liable to cause lactic acidosis.) -Patients with malnutrition, starvation, weakness, pituitary dysfunction or adrenal insufficiency(May cause hypoglycemia.) c)Persons who are contraindication of Cimetidine administration or need careful administration Patients with renal impairment, patients with hepatic impairment, patients with a history of drug hypersensitivity d)Persons who are contraindication of Dolutegravir administration or need careful administration Patients infected with hepatitis B or C virus (There is a possibility of worsening of liver function (increase or worsening of transaminases). e)Persons with hypotension (systolic blood pressure:=160 mmHg) f)Persons who donated or lost 200 mL (1 unit) of blood within 4 weeks before administration of study drugs or 400 mL (2 units) of blood within 3 months before administration of study drugs. g)Persons with a medical history/complication of severe nerve disease, cerebrovascular disease, liver disease, kidney disease, endocrine disease, cardiovascular disease, gastrointestinal disease (including digestive system disease which is considered to affect the absorption of study drugs), respiratory disease, metabolic disease, and anemia. h)Persons with estimated creatinine clearance (eClcr, Cockcroft-Gault Equation) <90 mL/min. The person with low renal excretion ability of medicines i)Persons who have been confirmed of a clinically severe abnormality based on medical examination or physical examination by the investigator or subinvestigator. j)Persons with a clinically severe disease within 30 days before administration of study drugs. k)Persons with lactose intolerance. l)Persons who took drugs, health food including St.John's wort, food 14 days prior to dosing and beverages including grapefruit, orange, and apple (including food containing them), and nutritional supplements 7 days prior to dosing and cannot comply with prohibition of taking them during the study. m)Persons who are smoking or taking nicotine within 30 days before administration of study drugs and who cannot comply with smoking cessation during the study period. n) Persons who took alcohol/caffeine-containing food on the day before hospitalization in each study period and cannot comply with prohibition of taking them until the day of discharge in each study period. o) Persons who tested positive in an alcohol breath test/urine drug test at screening. p) Persons who cannot discontinue the use of
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| -Kinetic parameters of endogenous substrates during administration / non-administration of metformin (OCT 2 and MATE probe), cimetidine (MATE 1/2K inhibitor) , dolutegravir (OCT 2 inhibitor). Measurement targets: Creatinine, N1-methylnicotinamide, N1-methyladenosine in plasma and urine, and other endogenous substrates of drug transporters and drug-metabolizing enzymes, including OCT2 and MATE1/2-K. -Evaluation of pharmacokinetics (PK) of metformin, cimetidine, dolutegravir Measurement target: metformin and cimetidine in plasma and urine, dolutegravir in plasma. -Analysis using the PBPK model Calculate the plasma concentration and urinary excretion rate of the test compound using the PBPK model. The difference between the calculated results and the measured values is evaluated by sum of least squares. | — |
Secondary
| Measure | Time frame |
|---|---|
| Kinetic parameters of other metabolites in plasma and urine samples | — |
Contacts
Public ContactYumi Morita
Keikokai Medical Corp P-One Clinic
Outcome results
None listed