Assessing the PK of Met DR, Met IR, and Met XR in Healthy Subjects

Healthy Subjects Clinical Trial

Official title:

A Randomized, Crossover Study Assessing the Pharmacokinetics of EFB0027 Versus ETB0015 and ETB0014 in Healthy Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02291510
• Other study ID #: LCRM103
• Status: Completed
• Phase: Phase 1
• First received: November 11, 2014
• Last updated: September 18, 2015
• Start date: October 2012
• Est. completion date: December 2012

Study information

• Verified date: September 2015
• Source: Elcelyx Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: December 2012
• Est. primary completion date: December 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 19 Years to 65 Years

Eligibility

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)

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Crossover Assignment, Masking: Single Blind (Subject), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Healthy Subjects

Intervention

Drug:
• Met DR
metformin delayed-release tablets
• Met XR
metformin extended-release tablets
• Met IR
metformin immediate-release tablets

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Elcelyx Therapeutics, Inc.

References & Publications (2)

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. — View 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.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	AUC (0-t) of Plasma Metformin	AUC (0-t) = Area under the curve from the first dose of study medication administration (0 h) to the time of the last quantifiable concentration following dose administration	from the time of dosing (0 h) to 36 hours post first dose	No
Primary	Cmax of Plasma Metformin	Cmax = Maximum concentration from the first dose of study medication administration (0 h) to the time of the last quantifiable concentration following dose administration	from the time of dosing (0 h) to 36 hours post first dose	No