Type 2 Diabetes MellitusPhase 1/2NCT01677299

Assessing the PK and Effect on Glucose and GI Hormone Concentrations of Metformin Delayed-Release in Subjects With T2DM

A Phase 1/2 study testing EFB0027 (metformin delayed release) and EFB0026 (metformin immediate-release) in people with Type 2 Diabetes Mellitus, run by Elcelyx Therapeutics, Inc. at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

This study will evaluate how EFB0027 and EFB0026 behave in subjects with type 2 diabetes mellitus. In addition, this study will compare the effects of EFB0027 and EFB0026 on circulating concentrations of glucose and gastrointestinal hormones in subjects with type 2 diabetes mellitus. Read more about this study

Who is it for?: Ages 19 to 70 years
Conditions the study is for: Type 2 Diabetes Mellitus
What is being tested?: EFB0027 (metformin delayed release) and EFB0026 (metformin immediate-release)
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 24 participants
Where: 2 sitesUnited States
Study dates: May 2012to Sep 2012
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 19 to 70 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Is 19 to 70 (inclusive) years old at Visit 1 (Screening).
Is diagnosed with Type 2 Diabetes Mellitus with
HbA1c between 6.0 to 9.5% (inclusive) for subjects managing their diabetes with:
Diet and exercise alone, or ii. A stable regimen (minimum of 2 months at Visit 1) of metformin alone, or iii. A stable regimen (minimum of 2 months at Visit 1) of DPP-4 inhibitor alone, OR
HbA1c between 6.0 to 8.5% (inclusive) for subjects managing their diabetes with a stable (minimum of 2 months at Visit 1) combination regimen of metformin and DPP-4 inhibitors.
Has serum creatinine below the upper limit of normal at Visit 1 and an estimated creatinine clearance above 80 using the Crockroft and Gault equation (CrCl = [(140 - age) x body weight in kg] / (serum creatinine x 72) x (0.85 for females) [ref. 3].

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Has a body mass index (BMI) of 25.0 to 40.0 kg/m^2 (inclusive) at Screening.
Is male, or is female and meets all of the following criteria:
Not breastfeeding
Negative pregnancy test result (human chorionic gonadotropin, beta subunit) at Visit 1 (Screening) (not applicable to hysterectomized females)
Surgically sterile, postmenopausal, or if of childbearing potential, must practice and be willing to continue to practice appropriate birth control during the entire duration of the study
Has a physical examination with no clinically significant abnormalities as judged by the investigator.
Ability to understand and willingness to adhere to protocol requirements.
If on chronic thyroid pharmacologic therapy, the dose must be stable for at least 3 months prior to Visit 1 (Screening), and must have thyroid-stimulating hormone (TSH) test result in normal range at Visit 1 (Screening).

Who cannot join

Has a clinically significant medical condition that could potentially affect study participation and/or personal well-being, as judged by the investigator, including but not limited to the following conditions:
Hepatic disease
Renal disease
Gastrointestinal disease
Endocrine disorder except diabetes
Cardiovascular disease

Show all 25Show fewer

Seizure disorder
Organ transplantation
Chronic infection
Has any chronic disease requiring medication that has been adjusted in the past 90 days (subjects may take acute intermittent over-the-counter medications such as Tylenol, if needed).
Has 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).
Has had major surgery of any kind within 6 months of Visit 1 (Screening).
Has received a blood transfusion within 6 months of Visit 1 (Screening).
Has a history of >5 kg weight change within 3 months of Visit 1 (Screening).
Has clinical laboratory test (clinical chemistry, hematology, or urinalysis) abnormalities other than those expected in subjects with diabetes and judged by the investigator to be clinically significant at Visit 1 (Screening).
Has physical, psychological, or historical finding that, in the investigator's opinion, would make the subject unsuitable for the study.
Currently abuses drugs or alcohol or has a history of abuse that in the investigator's opinion would cause the individual to be noncompliant with study procedures.
Has donated blood within 2 months of Visit 1 (Screening) or is planning to donate blood during the study.
Has used insulin within 3 months of Visit 1 (Screening).
Has received GLP-1 receptor agonists and/or thiazolidinedione treatment within 6 months of Visit 1 (Screening).
Has known intolerance to metformin.
Has received any investigational drug within 1 month (or five half-lives of the investigational drug, whichever is greater) of Visit 1 (Screening).
Has known allergies or hypersensitivity to any component of study treatment.
Is employed by Elcelyx Therapeutics, Inc (that is an employee, temporary contract worker, or designee of the company).
Smokes more than 10 cigarettes per day, 2 cigars per day, or uses more than 1 can of smokeless tobacco per week.

Trial locations and contacts

2 sites in 1 country.

United States2 sites

Celerion, Inc.
Lincoln, Nebraska, 68502
Celerion, Inc.
Tempe, Arizona, 85283

Other trials in United States

About this study

Official title: A Randomized, Crossover Study Assessing the Effects of pH 6.5 Enteric Coating of Metformin HCl Tablets on Pharmacokinetics and Changes in Circulating Glucose and Gastrointestinal Hormone Concentrations in Subjects With Type 2 Diabetes Mellitus

This study will evaluate how EFB0027 and EFB0026 behave in subjects with type 2 diabetes mellitus.

In addition, this study will compare the effects of EFB0027 and EFB0026 on circulating concentrations of glucose and gastrointestinal hormones in subjects with type 2 diabetes mellitus.

Conditions: Type 2 Diabetes Mellitus
Being tested: EFB0027 (metformin delayed release), EFB0026 (metformin immediate-release)
Medical subject headings: Diabetes Mellitus, Type 2

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

EFB0027 (metformin delayed release)Drug
Also called Met DR
Comparison of enteric-coating to assess effect on PK
EFB0026 (metformin immediate-release)Drug
Also called Met IR, metformin, Glucophage
Active comparator

Study groups in NCT01677299
Study group	Role	What they receive
1000 mg EFB0026 (metformin immediate-release)	Active comparator	BID Receives: Drug: EFB0026 (metformin immediate-release)
1000 mg EFB0027 (metformin delayed-release)	Experimental	BID Receives: Drug: EFB0027 (metformin delayed release)
500 mg EFB0027 (metformin delayed-release)	Experimental	BID Receives: Drug: EFB0027 (metformin delayed release)
500 mg EFB0026 + 1000 mg EFB0027	Experimental	BID Receives: Drug: EFB0027 (metformin delayed release); Drug: EFB0026 (metformin immediate-release)

What is being measured

The primary outcome is the main question the study is designed to answer.

Area Under the Curve (0-t) of Plasma Metformin
Measures from the time of dosing (0 h) to the time of the last quantifiable concentration following dose administration. The dose of study medication was administered at t = -1 min relative to the start time of the standardized breakfast.
Measured: Time points at which data were collected to create the area under the curve (0-t) for plasma metformin were: t = -0.08, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, and 11 h relative to the start time of the standardized breakfast.
Change in Fasting Plasma Glucose
LS mean difference from Baseline (Day 1) to Day 5
Measured: Change from Baseline (Day 1) to Day 5
Within Treatment Comparison Based on Ratios of AUCs of GLP-1
Measured: Ratio of Day 5 to Baseline
Within Treatment Comparison Based on Ratios of AUCs of PYY
Measured: Ratio of Day 5 to Baseline

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

May 2012Sep 2012

First posted3 Sep 2012 (estimated)
Study startMay 2012
Primary completionSep 2012
Study completionSep 2012

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Type 2 Diabetes MellitusStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Basic science
Allocation: Randomised
Intervention model: Crossover
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 24 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01677299
Sponsor's protocol ID: LCPOC10
Status last verified: Aug 2016
First submitted: 23 Aug 2012
Last updated: 20 Sep 2016
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

DeFronzo RA, Buse JB, Kim T, Burns C, Skare S, Baron A, Fineman M. Once-daily delayed-release metformin lowers plasma glucose and enhances fasting and postprandial GLP-1 and PYY: results from two randomised trials. Diabetologia. 2016 Aug;59(8):1645-54. doi: 10.1007/s00125-016-3992-6. Epub 2016 May 23.
PubMed 27216492

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Type 2 Diabetes Mellitus trials

Study at a glance

From the registry record, last updated by the sponsor on 20 Sep 2016. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomized, Crossover Study Assessing the Effects of pH 6.5 Enteric Coating of Metformin HCl Tablets on Pharmacokinetics and Changes in Circulating Glucose and Gastrointestinal Hormone Concentrations in Subjects With Type 2 Diabetes Mellitus
ClinicalTrials.gov ID: NCT01677299
Acronym / sponsor ID: LCPOC10
Conditions: Type 2 Diabetes Mellitus
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 24 participants (actual)
Lead sponsor: Elcelyx Therapeutics, Inc.Industry (pharma, biotech, devices)
Study start: May 2012
Primary completion: Sep 2012 (actual)
Study completion: Sep 2012 (actual)
First posted: 3 Sep 2012 (estimated)
Results: Posted 16 Jun 2014

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

This study will evaluate how EFB0027 and EFB0026 behave in subjects with type 2 diabetes mellitus.

In addition, this study will compare the effects of EFB0027 and EFB0026 on circulating concentrations of glucose and gastrointestinal hormones in subjects with type 2 diabetes mellitus.

Study design

Primary purpose: Basic science
Allocation: Randomised
Intervention model: Crossover
Masking: Double blind (participant, investigator)
Number of arms: 4

Arm	Type	Receives
1000 mg EFB0026 (metformin immediate-release)	Active comparator	Drug: EFB0026 (metformin immediate-release)BID
1000 mg EFB0027 (metformin delayed-release)	Experimental	Drug: EFB0027 (metformin delayed release)BID
500 mg EFB0027 (metformin delayed-release)	Experimental	Drug: EFB0027 (metformin delayed release)BID
500 mg EFB0026 + 1000 mg EFB0027	Experimental	Drug: EFB0027 (metformin delayed release), Drug: EFB0026 (metformin immediate-release)BID

Who may qualify

Ages: 19 to 70 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (14 listed)

Is 19 to 70 (inclusive) years old at Visit 1 (Screening).
Is diagnosed with Type 2 Diabetes Mellitus with
Has serum creatinine below the upper limit of normal at Visit 1 and an estimated creatinine clearance above 80 using the Crockroft and Gault equation (CrCl = [(140 - age) x body weight in kg] / (serum creatinine x 72) x (0.85 for females) [ref. 3].
Has a body mass index (BMI) of 25.0 to 40.0 kg/m^2 (inclusive) at Screening.
Is male, or is female and meets all of the following criteria:

Key exclusion criteria (25 listed)

Has a clinically significant medical condition that could potentially affect study participation and/or personal well-being, as judged by the investigator, including but not limited to the following conditions:
Has any chronic disease requiring medication that has been adjusted in the past 90 days (subjects may take acute intermittent over-the-counter medications such as Tylenol, if needed).
Has 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).
Has had major surgery of any kind within 6 months of Visit 1 (Screening).
Has received a blood transfusion within 6 months of Visit 1 (Screening).

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
EFB0027 (metformin delayed release)Also: Met DRComparison of enteric-coating to assess effect on PK	Drug	1000 mg EFB0027 (metformin delayed-release), 500 mg EFB0026 + 1000 mg EFB0027, 500 mg EFB0027 (metformin delayed-release)
EFB0026 (metformin immediate-release)Also: Met IR, metformin, GlucophageActive comparator	Drug	1000 mg EFB0026 (metformin immediate-release), 500 mg EFB0026 + 1000 mg EFB0027

Primary outcome

Area Under the Curve (0-t) of Plasma Metformin
Time frame: Time points at which data were collected to create the area under the curve (0-t) for plasma metformin were: t = -0.08, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, and 11 h relative to the start time of the standardized breakfast.
Measures from the time of dosing (0 h) to the time of the last quantifiable concentration following dose administration. The dose of study medication was administered at t = -1 min relative to the start time of the standardized breakfast.
Change in Fasting Plasma Glucose
Time frame: Change from Baseline (Day 1) to Day 5
LS mean difference from Baseline (Day 1) to Day 5
Within Treatment Comparison Based on Ratios of AUCs of GLP-1
Time frame: Ratio of Day 5 to Baseline
Within Treatment Comparison Based on Ratios of AUCs of PYY
Time frame: Ratio of Day 5 to Baseline

Results and safety

Results posted to the registry on 16 Jun 2014, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Sequence 1: BCAD	6	6
Sequence 2: ABDC	6	3
Sequence 3: CDBA	6	5
Sequence 4: DACB	6	5

Primary outcome: Area Under the Curve (0-t) of Plasma Metformin

Time frame: Time points at which data were collected to create the area under the curve (0-t) for plasma metformin were: t = -0.08, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, and 11 h relative to the start time of the standardized breakfast.. Mean (Standard Deviation). Unit: ng*h/mL

Measure	1000 mg EFB0026 n = 19	1000 mg EFB0027 n = 19	500 mg EFB0027 n = 19	500 mg EFB0026 + 1000 mg EFB0027 n = 19
Value	8672 (29.7)	4774 (29.9)	3842 (37.6)	8075 (38.6)

Population analysed: Evaluable Population

Primary outcome: Change in Fasting Plasma Glucose

Time frame: Change from Baseline (Day 1) to Day 5. Least squares mean (Standard Error). Unit: mg/dL

Measure	1000 mg EFB0026 n = 19	1000 mg EFB0027 n = 19	500 mg EFB0027 n = 19	500 mg EFB0026 + 1000 mg EFB0027 n = 19
Value	-22.5 (6.8)	-19.9 (5)	-16.4 (3.8)	-21.2 (4.7)

1000 mg EFB0026: LS mean diff (Day 5 - Baseline): -22.5 (95% CI -37 to -8), p <0.05, Mixed Models Analysis
1000 mg EFB0027: LS mean diff (Day 5 - Baseline): -20 (95% CI -30 to -9), p <0.05, Mixed Models Analysis
500 mg EFB0027: LS mean diff (Day 5 - Baseline): -16 (95% CI -24 to -8), p <0.05, Mixed Models Analysis

Population analysed: Evaluable Population

Primary outcome: Within Treatment Comparison Based on Ratios of AUCs of GLP-1

Time frame: Ratio of Day 5 to Baseline. Least squares mean (Standard Error). Unit: none (values are ratios)

Measure	1000 mg EFB0026 n = 19	1000 mg EFB0027 n = 19	500 mg EFB0027 n = 19	500 mg EFB0026 + 1000 mg EFB0027 n = 19
Value	1.87 (0.18)	1.62 (.11)	1.69 (.15)	1.88 (.19)

1000 mg EFB0027: Geometric LS mean ration: 1.6 (95% CI 1.4 to 1.9), p <0.05, Mixed Models Analysis
1000 mg EFB0026: Geo LSmean ratio of (Day 5/Baseline): 1.9 (95% CI 1.5 to 2.3), p <0.05, Mixed Models Analysis
500 mg EFB0027: Geo LSmean ratio (Day 5/Baseline): 1.7 (95% CI 1.4 to 2.0), p <0.05, Mixed Models Analysis

Population analysed: Evaluable

Primary outcome: Within Treatment Comparison Based on Ratios of AUCs of PYY

Time frame: Ratio of Day 5 to Baseline. Least squares mean (Standard Error). Unit: none (values are ratios)

Measure	1000 mg EFB0026 n = 19	1000 mg EFB0027 n = 19	500 mg EFB0027 n = 19	500 mg EFB0026 + 1000 mg EFB0027 n = 19
Value	1.55 (.09)	1.38 (.09)	1.46 (.06)	1.49 (.06)

1000 mg EFB0026: Geo LSmean ratio (Day 5/Baseline): 1.5 (95% CI 1.4 to 1.8), p <0.05, Mixed Models Analysis
1000 mg EFB0027: Geo LSmean ratio (Day 5/Baseline): 1.4 (95% CI 1.2 to 1.6), p <0.05, Mixed Models Analysis
500 mg EFB0027: Geo LSmean ratio (Day 5/Baseline): 1.5 (95% CI 1.3 to 1.6), p <0.05, Mixed Models Analysis

Population analysed: Evaluable Population

Adverse events

Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
1000 mg EFB0026 BID	0 of 22 (0%)	6 of 22 (27.3%)	Not reported
1000 mg EFB0027 BID	1 of 20 (5%)	5 of 20 (25%)	Not reported
500 mg EFB0027 BID	0 of 20 (0%)	4 of 20 (20%)	Not reported
500 mg EFB0026 BID Plus 1000 mg EFB0027 BID	0 of 21 (0%)	10 of 21 (47.6%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 20 Sep 2016.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 27216492DeFronzo RA, Buse JB, Kim T, Burns C, Skare S, Baron A, Fineman M. Once-daily delayed-release metformin lowers plasma glucose and enhances fasting and postprandial GLP-1 and PYY: results from two randomised trials. Diabetologia. 2016 Aug;59(8):1645-54. doi: 10.1007/s00125-016-3992-6. Epub 2016 May 23.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

2 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 20 Sep 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 16 Jun 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Area Under the Curve (0-t) of Plasma Metformin (time frame: Time points at which data were collected to create the area under the curve (0-t) for plasma metformin were: t = -0.08, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, and 11 h relative to the start time of the standardized breakfast.). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01677299, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Sep 2016.