Type 2 Diabetes MellitusPhase 2NCT01819272

Assessing the Efficacy, Safety, and Tolerability of Met DR in Subjects With T2DM Over 12 Weeks

A Phase 2 study testing Met DR and Met XR in people with Type 2 Diabetes Mellitus, run by Elcelyx Therapeutics, Inc..

Completed

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

Trial summary

This study compared the effect of delayed-release metformin (Met DR) to placebo and extended release metformin (Met XR) on glycemic control (fasting plasma glucose and HbA1c) and body weight, and assessed the safety and tolerability of a range of doses of Met DR when administered in subjects with type 2 diabetes… Read more about this study

Who is it for?: Ages 18 to 65 years
Conditions the study is for: Type 2 Diabetes Mellitus
What is being tested?: Met DR and Met XR
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 240 participants
Where: No sites listed yet
Study dates: Apr 2013to Sep 2013
Phase: Phase 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 18 to 65 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Male or female with T2DM who was ≥18 and ≤65 years of age at Visit 1
Had a body mass index (BMI) of 25.0 kg/m² to 45.0 kg/m², inclusive, at Visit 1
Screening HbA1c 7.0 to 9.5% (inclusive) at Visit 1 if treated with diet and exercise alone, or 6.0 to 9.5% (inclusive) if on a stable dose of either metformin or DPP-4 inhibitor monotherapy for a minimum of 2 months at Visit 1, or a combination of these 2 agents only on a stable regimen for a minimum of 2 months at Visit 1
Had serum creatinine concentration of <1.5 mg/dL (male) or <1.4 mg/dL (female) and an estimated glomerular filtration rate (eGFR) of ≥60 mL/min/1.73 m² based on the Modification of Diet in Renal Disease (MDRD) equation
Had a fasting glucose concentration of <280 mg/dL at Visit 1
Had a stable body weight, i.e., not varying by >5% for at least 6 months prior to Visit 1 as documented by the investigator

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Was male, or if female and met all of the following criteria:
Not breastfeeding
Negative pregnancy test result (human chorionic gonadotropin, beta subunit [βhCG]) at Visit 1 (not applicable to hysterectomized females)
If of child bearing potential (including perimenopausal women who have had a menstrual period within 1 year), must have practiced and be willing to continue to practice appropriate birth control during the entire duration of the study
Had a physical examination and ECG with no clinically significant abnormalities as judged by the investigator at Visit 1
Had no clinically significant laboratory test values (clinical chemistry, hematology, urinalysis) other than those expected in subjects with diabetes as judged by the investigator at Visit 1
Either was not treated with or had been on a stable treatment regimen with any of the following medications for a minimum of 2 months prior to Visit 1:
Hormone replacement therapy (female subjects)
Oral contraceptives (female subjects)
Antihypertensive agents
Lipid-lowering agents
Thyroid replacement therapy
Antidepressant agents
Testosterone therapy (male subjects)
If on chronic thyroid pharmacologic therapy, had a serum thyroid-stimulating hormone test result within the normal range at Visit 1
Was willing and able to follow study procedures
Was able to read, understand, and sign the Informed Consent Form and an Authorization to Use and Disclose Protected Health Information form, answer the study questions, communicate with the investigator, and understand and comply with protocol requirements

Who cannot join

Had 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 T2DM
Cardiovascular disease

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Central nervous system diseases
Psychiatric or neurological disorders
Organ transplantation
Chronic or acute infection (e.g., tuberculosis, human immunodeficiency virus, hepatitis B virus, or hepatitis C virus)
Orthostatic hypotension, fainting spells or blackouts
Allergy or hypersensitivity
Clinically significant malignant disease (with the exception of basal and squamous cell carcinoma of the skin) within 5 years of Visit 1
Had known hypersensitivity, intolerability, or allergies to metformin HCl or any component of study treatment
Had a physical, psychological, or historical finding that, in the investigator's opinion, would make the subject unsuitable for the study
Current drugs or alcohol abuse or had a history of abuse that in the investigator's opinion would cause the individual to be noncompliant with study procedures
Had major surgery or a blood transfusion within 2 months of Visit 1 or was planning to donate blood during the study, or had a significant blood loss within 2 months prior to Visit 1
Had been treated, was being treated, or was expected to require or undergo treatment with any of the following excluded medications:
Insulin or sulphonylurea treatment within 3 months of Visit 1
GLP-1 receptor agonists and/or thiazolidinedione treatment within 6 months of Visit 1
Nifedipine within 3 months of Visit 1
Systemic corticosteroids by oral, intravenous, intra-articular, or intra-muscular route within 30 days of screening or for more than 1 week within 3 months of Visit 1
Prescription weight loss medications within 3 months of Visit 1
Chronic or frequent use, in the judgment of the investigator, of any drug treatment that affects gastric pH (prescription or over-the-counter), including proton pump inhibitors or any antacids or medications such as Rolaids or Pepcid within 1 month of Visit 1
Had received or planned to receive any iodinated contrast dye within 1 week prior to Visit 1 (Screening)
Had a surgical gastrointestinal procedure that may impact the gut hormonal response to study medication
History or presence of inflammatory bowel disease or other severe gastrointestinal disease, particularly those which may impact gastric emptying, such as gastroparesis, pyloric stenosis, gastric bypass surgery or gastric banding surgery
Had received any investigational drug within 30 days (or five half-lives of the investigational drug, whichever was greater) of Visit 1
Was an immediate family member (spouse, parent, child, or sibling; biological or legally adopted) of personnel directly affiliated with the study at the clinical study site, or was directly affiliated with the study at the clinical study site
Was employed by Elcelyx Therapeutics, Inc. (that is an employee, temporary contract worker, or designee responsible for the conduct of the study)

About this study

Official title: A 12-Week, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter Study to Assess the Efficacy, Safety, and Tolerability of Delayed-Release Metformin in Subjects With Type 2 Diabetes Mellitus

Conditions: Type 2 Diabetes Mellitus
Being tested: Met DR, Met XR, Placebo
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.

Met DRDrug
metformin delayed-release tablets
Met XRDrug
metformin extended-release tablets
PlaceboDrug
placebo delayed-release tablets

Study groups in NCT01819272
Study group	Role	What they receive
600 mg DR	Experimental	600 mg delayed-release metformin once daily in the morning Receives: Drug: Met DR
800 mg DR	Experimental	800 mg delayed-release metformin once daily in the morning Receives: Drug: Met DR
1000 mg DR	Experimental	1000 mg delayed-release metformin once daily in the morning Receives: Drug: Met DR
1000 mg XR	Active comparator	1000 mg extended-release metformin once daily in the evening Receives: Drug: Met XR
2000 mg XR	Active comparator	2000 mg extended-release metformin once daily in the evening Receives: Drug: Met XR
Placebo	Placebo comparator	Placebo once daily in the morning Receives: Drug: Placebo

What is being measured

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

Change in Fasting Plasma Glucose (mg/dL) at 4 Weeks
Measured: Baseline and 4 weeks after the first dose of study medication

Secondary outcomes (2)

AUC4-12wk of Change in Fasting Plasma Glucose (mg/dL*Week) Concentrations From Baseline to 12 Weeks
Measured: Baseline and 4 to 12 weeks after the first dose of study medication
Change in HbA1c (%) at 12 Weeks
Measured: Baseline and 12 weeks after the first dose of study medication

Timeline

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

Apr 2013Sep 2013

First posted27 Mar 2013 (estimated)
Study startApr 2013
Primary completionSep 2013
Study completionSep 2013

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 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 240 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01819272
Sponsor's protocol ID: LCRM105
Status last verified: Feb 2017
First submitted: 19 Mar 2013
Last updated: 15 Mar 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

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.
PubMed 26285584

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?

Official record

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All Type 2 Diabetes Mellitus trials

Study at a glance

From the registry record, last updated by the sponsor on 15 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A 12-Week, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter Study to Assess the Efficacy, Safety, and Tolerability of Delayed-Release Metformin in Subjects With Type 2 Diabetes Mellitus
ClinicalTrials.gov ID: NCT01819272
Acronym / sponsor ID: LCRM105
Conditions: Type 2 Diabetes Mellitus
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 240 participants (actual)
Lead sponsor: Elcelyx Therapeutics, Inc.Industry (pharma, biotech, devices)
Study start: Apr 2013
Primary completion: Sep 2013 (actual)
Study completion: Sep 2013 (actual)
First posted: 27 Mar 2013 (estimated)
Results: Posted 21 Sep 2015

Clinical summary

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

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 6

Arm	Type	Receives
600 mg DR	Experimental	Drug: Met DR600 mg delayed-release metformin once daily in the morning
800 mg DR	Experimental	Drug: Met DR800 mg delayed-release metformin once daily in the morning
1000 mg DR	Experimental	Drug: Met DR1000 mg delayed-release metformin once daily in the morning
1000 mg XR	Active comparator	Drug: Met XR1000 mg extended-release metformin once daily in the evening
2000 mg XR	Active comparator	Drug: Met XR2000 mg extended-release metformin once daily in the evening
Placebo	Placebo comparator	Drug: PlaceboPlacebo once daily in the morning

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (23 listed)

Male or female with T2DM who was ≥18 and ≤65 years of age at Visit 1
Had a body mass index (BMI) of 25.0 kg/m² to 45.0 kg/m², inclusive, at Visit 1
Screening HbA1c 7.0 to 9.5% (inclusive) at Visit 1 if treated with diet and exercise alone, or 6.0 to 9.5% (inclusive) if on a stable dose of either metformin or DPP-4 inhibitor monotherapy for a minimum of 2 months at Visit 1, or a combination of these 2 agents only on a stable regimen for a minimum of 2 months at Visit 1
Had serum creatinine concentration of <1.5 mg/dL (male) or <1.4 mg/dL (female) and an estimated glomerular filtration rate (eGFR) of ≥60 mL/min/1.73 m² based on the Modification of Diet in Renal Disease (MDRD) equation
Had a fasting glucose concentration of <280 mg/dL at Visit 1

Key exclusion criteria (30 listed)

Had 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:
Clinically significant malignant disease (with the exception of basal and squamous cell carcinoma of the skin) within 5 years of Visit 1
Had known hypersensitivity, intolerability, or allergies to metformin HCl or any component of study treatment
Had a physical, psychological, or historical finding that, in the investigator's opinion, would make the subject unsuitable for the study
Current drugs or alcohol abuse or had a history of abuse that in the investigator's opinion would cause the individual to be noncompliant with study procedures

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
Met DRmetformin delayed-release tablets	Drug	1000 mg DR, 600 mg DR, 800 mg DR
Met XRmetformin extended-release tablets	Drug	1000 mg XR, 2000 mg XR
Placeboplacebo delayed-release tablets	Drug	Placebo

Primary outcome

Change in Fasting Plasma Glucose (mg/dL) at 4 Weeks
Time frame: Baseline and 4 weeks after the first dose of study medication

2 secondary outcomes

AUC4-12wk of Change in Fasting Plasma Glucose (mg/dL*Week) Concentrations From Baseline to 12 Weeks
Time frame: Baseline and 4 to 12 weeks after the first dose of study medication
Change in HbA1c (%) at 12 Weeks
Time frame: Baseline and 12 weeks after the first dose of study medication

Results and safety

Results posted to the registry on 21 Sep 2015, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Placebo	41	35
600 mg DR	39	36
800 mg DR	40	37
1000 mg DR	40	35
1000 mg XR	40	36
2000 mg XR	40	33

Primary outcome: Change in Fasting Plasma Glucose (mg/dL) at 4 Weeks

Time frame: Baseline and 4 weeks after the first dose of study medication. Median (Full Range). Unit: mg/dL

Measure	Placebo n = 37	600 mg DR n = 35	800 mg DR n = 37	1000 mg DR n = 36	1000 mg XR n = 35	2000 mg XR n = 35
Value	-4 (-69 to 48)	-11 (-124 to 150)	-13 (-62 to 145)	-18 (-90 to 113)	-12 (-111 to 58)	-25 (-110 to 20)

Placebo vs 600 mg DR: Hodges-Lehmann Estimation: -9.0 (95% CI -21.0 to 1.0), p = 0.0670, Kruskal-Wallis
Placebo vs 800 mg DR: Hodges-Lehmann Estimation: -14.0 (95% CI -22.0 to -4.0), p = 0.0057, Kruskal-Wallis
Placebo vs 1000 mg DR: Hodges-Lehmann Estimation: -12.0 (95% CI -25.0 to 3.0), p = 0.1095, Kruskal-Wallis

Population analysed: Week 4 Evaluable

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: Approximately 83 to 107 days depending on the number of intervening days between study visits. Other adverse events reported at 4% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Placebo	0 of 41 (0%)	9 of 41 (22%)	Not reported
600 mg DR	1 of 39 (2.6%)	9 of 39 (23.1%)	Not reported
800 mg DR	0 of 40 (0%)	11 of 40 (27.5%)	Not reported
1000 mg DR	2 of 40 (5%)	9 of 40 (22.5%)	Not reported
1000 mg XR	1 of 40 (2.5%)	8 of 40 (20%)	Not reported
2000 mg XR	0 of 40 (0%)	8 of 40 (20%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 15 Mar 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 26285584Buse 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.

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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.

Andrew Lewin principal investigator

National Research Institute - Wilshire

Rubin Saavedra principal investigator

Alliance Against Diabetes / AAD Clinical Research

Lydie Hazan principal investigator

Axis Clinical Trials

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Met DR and Met XR in people with Type 2 Diabetes Mellitus, run by Elcelyx Therapeutics, Inc..

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 23 inclusion and 30 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 15 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

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

What does this phase mean?

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 21 Sep 2015). 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?

Change in Fasting Plasma Glucose (mg/dL) at 4 Weeks (time frame: Baseline and 4 weeks after the first dose of study medication). 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 NCT01819272, 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 15 Mar 2017.