PK Study Comparing Metformin Eicosapentaenoate to a Combined Dose of Metformin Hydrochloride and Ethyl Ester EPA

Study Overview
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Brief Summary
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The primary objective of the study is to contrast the pharmacokinetic profiles of metformin and EPA delivered separately as co-administered products (metformin hydrochloride or Glucophage and icosapent ethyl or Vascepa) and together as the solid dose form (metformin eicosapentaenoate or TP-101) under fasted and fed conditions. A secondary objective is to evaluate the safety and tolerability of single and repeat single doses of TP-101.

Official Title
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An Open-label, Single and Repeat Single Ascending Dose Escalation Study to Compare the Pharmacokinetics of Metformin Eicosapentaenoate With Metformin Hydrochloride and Icosapent Ethyl Following Oral Administration to Healthy Volunteers

Conditions
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Diabetes Mellitus, Non-Insulin-Dependent, Hypertriglyceridemia

Intervention / Treatment
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* Drug: Metformin Eicosapentaenoate
* Drug: Metformin HCl and Vascepa


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent executed prior to protocol screening assessments; Men or women 18 to 65 years of age, inclusive (Women may be surgically sterile via tubal ligation, bilateral oophorectomy or hysterectomy or who are postmenopausal for >1 year. Women who are of childbearing potential must agree to practice adequate contraception one month before the first dose of study medication and up to Day 16 of the study. Adequate contraception may include, but is not limited to, abstinence, monogamous relationship with vasectomized partner, barrier methods such as condoms or diaphragms with spermicide or foam, intrauterine devices, and licensed hormonal methods.); No history of chronic diseases, except for subjects with well-controlled hypertension or well-controlled hyperlipidemia; BMI ≤30kg/m2; No significant medical history including diabetes or hypertension complicated by hyperlipidemia (metabolic syndrome); Negative urine drug and alcohol tests at Screening; and, No metformin or omega-3 products within 2 months. Exclusion Criteria: Abnormal findings on physical examination, EKG, vital signs, and clinical laboratory testing, in the judgment of the investigator; Allergies to fish or shellfish; Impaired renal function (calculated eGFR <60 mL/min); Abnormal laboratory values for T3, T4 and TSH at the Screening Visit; Aspartate aminotransferase/alanine aminotransferase (AST/ALT) >2x upper limits of normal (ULN) or serum bilirubin >1.5 mg/dL; Requirement of prescription medication within 14 days of the Screening Visit, with the exception of prescription medications for the prevention of pregnancy, anti hypertensives for hypertension, or statins for hyperlipidemia. Doses of one or two anti-hypertensives and/or a statin must be stable for >1 month; Normal doses of over-the-counter medications, including vitamins are allowed but not within 3 days of Visit 2 (first day of dosing); Current or history of abuse of alcohol or illicit drugs within the preceding year to the Screening Visit; Participation in a dietary modification or an intensive weight loss program; Participation in another clinical trial of an investigational product within 3 months prior to the Screening Visit; Smokers (use of tobacco in the past 3 months); or, Donation or loss of 400 mL blood or more in the last 8 weeks.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Cohort A - Low Dose<br>Metformin Eicosapentaenoate 1500 mg or Metformin HCl 500 mg and Vascepa 1000 mg | Drug: Metformin Eicosapentaenoate<br> <br> Drug: Metformin HCl and Vascepa<br> <br> |
| Active Comparator: Cohort B - High Dose<br>Metformin Eicosapentaenoate 3000 mg or Metformin HCl 1000 mg and Vascepa 2000 mg | Drug: Metformin Eicosapentaenoate<br> <br> Drug: Metformin HCl and Vascepa<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC following single and repeat single oral administration of metformin eicosapentaenoate, metformin hydrochloride and Vascepa |  | PK samples at 0, 0.5, 1, 2, 4, 8, and 12 hours following drug administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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EPA, Type 2 diabetes, T2DM, hypertriglyceridemia, severe hypertriglyceridemia, dyslipidemia, triglycerides, lipids, omega-3 fatty acids, ethyl-EPA, Metformin, Glucophage, Lovaza, Vascepa, Epanova, Astra Zeneca, Amarin, GSK