Clinical trial NCT02291510: Assessing the PK of Met DR, Met IR, and Met XR in Healthy Subjects
Official title: A Randomized, Crossover Study Assessing the Pharmacokinetics of EFB0027 Versus ETB0015 and ETB0014 in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Subjects
Lead sponsor: Elcelyx Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2014-11-14
Enrollment: 20
Sex: ALL
Minimum age (years): 19
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: Inclusion Criteria:

1. 19 to 65 (inclusive) years old at Visit 1 (Screening)
2. Male, or if female and met all of the following criteria:

   1. Not breastfeeding
   2. Negative pregnancy test result at Visit 1 (Screening) (not applicable to hysterectomized females)
   3. 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
3. Body mass index (BMI) of 25.0 to 35.0 kg/m² (inclusive) at Visit 1 (Screening)
4. Had a physical examination with no clinically significant abnormalities as judged by the investigator
5. 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
6. Ability to understand and willingness to adhere to protocol requirements

Exclusion Criteria:

1. 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:

   1. Hepatic disease
   2. Gastrointestinal disease
   3. Endocrine disorder (including diabetes and impaired glucose tolerance)
   4. Cardiovascular disease
   5. Central nervous system diseases
   6. Psychiatric or neurological disorders
   7. Organ transplantation
   8. Chronic or acute infection
   9. Orthostatic hypotension, fainting spells or blackouts
   10. Allergy or hypersensitivity
2. 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)
3. Had major surgery of any kind within 6 months of Visit 1 (Screening)
4. Had a history of \>6 kg weight change within 3 months of Visit 1 (Screening)
5. Had clinical laboratory test (clinical chemistry, hematology, or urinalysis) abnormalities judged by the investigator to be clinically significant at Visit 1 (Screening)
6. Had a physical, psychological, or historical finding that, in the investigator's opinion, would make the subject unsuitable for the study
7. 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)
8. 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
9. 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
10. 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
11. 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
12. Had known allergies or hypersensitivity to any component of study treatment
13. Was employed by Elcelyx Therapeutics, Inc (that is an employee, temporary contract worker, or designee of the company)

Primary outcomes:
measure: AUC (0-t) of Plasma Metformin
timeFrame: 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.
measure: Cmax of Plasma Metformin
timeFrame: 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.
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: Celerion
name: Scott Rasmussen, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: DeFronzo RA, Buse JB, Kim T, Skare S, Baron A, Fineman M, editors. Dissociation between Metformin Plasma Exposure and its Glucose-Lowering Effect: A Novel Gut-Mediated Mechanism of Action. 73rd Annual Scientific Meeting of The American Diabetes Association; 2013 June 21-25th; Chicago, Il.
citation: Buse JB, DeFronzo RA, Rosenstock J, Kim T, Burns C, Skare S, Baron A, Fineman M. The Primary Glucose-Lowering Effect of Metformin Resides in the Gut, Not the Circulation: Results From Short-term Pharmacokinetic and 12-Week Dose-Ranging Studies. Diabetes Care. 2016 Feb;39(2):198-205. doi: 10.2337/dc15-0488. Epub 2015 Aug 18.