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

Phase 1

Completed

• Conditions: Healthy Subjects
• Interventions: Drug: Met DR; Drug: Met XR; Drug: Met IR

• Registration Number: NCT02291510
• Lead Sponsor: Elcelyx Therapeutics, Inc.

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2012-10
• Primary Completion: 2012-12
• Study Completion: 2012-12
• Study First Submitted: 2014-11-11
• Study First Submitted QC: 2014-11-13
• Study First Posted: 2014-11-14
• Results First Submitted: 2015-08-21
• Results First Submitted QC: 2015-08-21
• Results First Posted: 2015-09-21
• Status Verified: 2016-10
• Last Update Submitted: 2016-10-19
• Last Update Posted: 2016-12-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 20

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

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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)

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
1000 mg Met DR BID	Met DR	Two doses of 1000 mg metformin delayed-release
2000 mg Met XR QD	Met XR	Single dose of 2000 mg metformin extended-release
500 mg Met DR BID	Met DR	Two doses of 500 mg metformin delayed-release
1000 mg Met IR BID	Met IR	Two doses of 1000 mg metformin immediate-release

Primary Outcome Measures

Name	Time	Method
AUC (0-t) of Plasma Metformin	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 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.