A Randomized, Crossover Study Assessing the Pharmacokinetics of EFB0027 Versus ETB0015 and ETB0014 in Healthy Subjects
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Elcelyx Therapeutics, Inc.
- Enrollment
- 20
- Primary Endpoint
- AUC (0-t) of Plasma Metformin
Study Overview
Brief Summary
This study compared the pharmacokinetics (PK) and assessed the safety of delayed-release metformin (Met DR, EFB0027) at two dosage levels, immediate-release metformin (Met IR, ETB0015), and extended-release metformin (Met XR, ETB0014) in healthy subjects.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Basic Science
- Masking
- Single (Participant)
Eligibility Criteria
- Ages
- 19 Years to 65 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •19 to 65 (inclusive) years old at Visit 1 (Screening)
- •Male, or if female and met all of the following criteria:
- •Not breastfeeding
- •Negative pregnancy test result at Visit 1 (Screening) (not applicable to hysterectomized females)
- •Surgically sterile, postmenopausal, or if of childbearing potential, practiced and was willing to continue to practice appropriate birth control during the entire duration of the study
- •Body mass index (BMI) of 25.0 to 35.0 kg/m² (inclusive) at Visit 1 (Screening)
- •Had a physical examination with no clinically significant abnormalities as judged by the investigator
- •Had normal renal function with an estimated glomerular filtration rate (eGFR) ≥90 mL/min/1.73 m² based on the Modification of Diet in Renal Disease (MDRD) equation
- •Ability to understand and willingness to adhere to protocol requirements
Exclusion Criteria
- •Had a clinically significant medical condition as judged by the investigator that could potentially affect study participation and/or personal well-being, including but not limited to the following conditions:
- •Hepatic disease
- •Gastrointestinal disease
- •Endocrine disorder (including diabetes and impaired glucose tolerance)
- •Cardiovascular disease
- •Central nervous system diseases
- •Psychiatric or neurological disorders
- •Organ transplantation
- •Chronic or acute infection
- •Orthostatic hypotension, fainting spells or blackouts
- •Allergy or hypersensitivity
- •Had any chronic disease requiring medication that was adjusted in the past 90 days (subjects could take acute intermittent over-the-counter medications such as Tylenol, if needed)
- •Had major surgery of any kind within 6 months of Visit 1 (Screening)
- •Had a history of >6 kg weight change within 3 months of Visit 1 (Screening)
- •Had clinical laboratory test (clinical chemistry, hematology, or urinalysis) abnormalities judged by the investigator to be clinically significant at Visit 1 (Screening)
- •Had a physical, psychological, or historical finding that, in the investigator's opinion, would make the subject unsuitable for the study
- •Had any drug treatment that affects gastric pH (prescription or over-the-counter), including any antacids or medications such as Rolaids or Pepcid within 2 days of Visit 1 (Screening)
- •Currently abused drugs or alcohol or had a history of abuse that in the investigator's opinion would cause the individual to be noncompliant with study procedures
- •Smoked more than 10 cigarettes per day, 3 cigars per day, 3 pipes per day, used more than 1 can of smokeless tobacco per week, or used a combination of tobacco products that approximate nicotine doses equivalent to 10 cigarettes per day
- •Had donated blood within 3 months of the date of the first dose of randomized study medication, or was planning to donate blood during the study
- •Had received any investigational drug within 2 months (or five half-lives of the investigational drug, whichever was greater) of the date of the first dose of randomized study medication
- •Had known allergies or hypersensitivity to any component of study treatment
- •Was employed by Elcelyx Therapeutics, Inc (that is an employee, temporary contract worker, or designee of the company)
Arms & Interventions
500 mg Met DR BID
Two doses of 500 mg metformin delayed-release
Intervention: Met DR (Drug)
1000 mg Met DR BID
Two doses of 1000 mg metformin delayed-release
Intervention: Met DR (Drug)
1000 mg Met IR BID
Two doses of 1000 mg metformin immediate-release
Intervention: Met IR (Drug)
2000 mg Met XR QD
Single dose of 2000 mg metformin extended-release
Intervention: Met XR (Drug)
Outcomes
Primary Outcomes
AUC (0-t) of Plasma Metformin
Time Frame: Time points to create AUC (0-t) were: t = -0.08, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 11, 11.92, 12.5, 13, 13.5, 14, 14.5, 15, 16, 17, 18, 19, 20, 21, 22, 23, and 24 hours relative to the start time of the standardized dinner.
AUC (0-t) = Area under the curve from the time of dosing (0 h) to the time of the last quantifiable concentration after the standardized dinner. Doses were administered 1 min prior to 0 h (standardized dinner) for once daily in the evening (qPM) and twice daily (BID) dosing and 1 min prior to 12 h (standardized breakfast) for once daily in the morning (qAM) and BID dosing.
Cmax of Plasma Metformin
Time Frame: Time points to create Cmax were: t = -0.08, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 11, 11.92, 12.5, 13, 13.5, 14, 14.5, 15, 16, 17, 18, 19, 20, 21, 22, 23, and 24 hours relative to the start time of the standardized dinner.
Cmax = Maximum concentration from the first dose of study medication administration (0 h) to the time of the last quantifiable concentration following dose administration. Doses were administered 1 min prior to 0 h (standardized dinner) for qPM and BID dosing and 1 min prior to 12 h (standardized breakfast) for qAM and BID dosing.
Secondary Outcomes
No secondary outcomes reported