Renal InsufficiencyPhase 2NCT01658514

Assessing the Behavior of Met DR in Subjects With Kidney Dysfunction

A Phase 2 study testing Met DR and Met XR in people with Renal Insufficiency, run by Elcelyx Therapeutics, Inc..

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

Who is it for?: Ages 18 to 80 yearsHealthy volunteers can take part
Conditions the study is for: Renal Insufficiency
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: 39 participants
Where: No sites listed yet
Study dates: Jan 2014to Jun 2014
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 80 years
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

18 to 80 (inclusive) years old at Visit 1 (Screening)
Male, or female and met all of the following criteria:
Not breastfeeding
Negative pregnancy test result at Visit 1 (Screening) (not applicable to postmenopausal or surgically sterile females)
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
Body weight of ≥45 kg

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Body mass index (BMI) of 18.0 to 40.0 kg/m² (inclusive) at Visit 1 (Screening)
Had type 2 diabetes mellitus and an HbA1c ≤10.0%
Had a physical examination with no clinically significant abnormalities as judged by the investigator
Estimated glomerular filtration rate (eGFR) ≥15 mL/min/1.73 m² based on the Modification of Diet in Renal Disease (MDRD) equation
Ability to understand and willingness to adhere to protocol requirements

Who cannot join

Had End Stage Renal Disease requiring dialysis or severe renal dysfunction with eGFR <15 mL/min/1.73 m²
Was on dialysis or had been on dialysis within 12 months of Visit 1 (Screening)
Had received or planned to receive any iodinated contrast dye within 1 week prior to Visit 1 (Screening) or after study medication administration
Was taking or had taken within 1 week of Visit 1 cationic drugs that are eliminated by renal tubular secretion (e.g., amiloride, digoxin, morphine, procainamide, quinidine, quinine, ranitidine, triamterene, trimethoprim, and vancomycin)
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

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Gastrointestinal disease
Endocrine disorder (type 2 diabetes mellitus was allowed)
Cardiovascular disease
Central nervous system diseases
Psychiatric or neurological disorders
Organ transplantation
Chronic or acute infection
Orthostatic hypotension, fainting spells or blackouts
Allergy or hypersensitivity
Had any chronic disease requiring medication that had been adjusted in the past 14 days (subjects could take acute intermittent over-the-counter medications such as Tylenol, if needed)
Had major surgery of any kind within 6 months of Visit 1 (Screening)
Had a clinically significant finding of an electrocardiogram (ECG) as assessed by the investigator at Visit 1 (Screening)
Had clinical laboratory test (clinical chemistry, hematology, or urinalysis) abnormalities, other than those related to diabetes or renal disease and other stable diseases, judged by the investigator to be clinically significant at Visit 1 (Screening)
Had a hemoglobin result <8 g/dL or a level indicating severe anemia of renal origin
Had a physical, psychological, or historical finding that, in the investigator's opinion, would make the subject unsuitable for the study
Had received Byetta® or short-acting insulin within 3 days of Visit 1 (Screening)
Had received metformin within 4 weeks of Visit 1 (Screening)
Had any drug treatment that affects gastrointestinal motility or gastric pH (prescription or over-the-counter), including any antacids or medications such as Rolaids or Pepcid, within 2 days of Visit 2
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
Smoked more than 10 cigarettes, 3 cigars, or 3 pipes per day
Had donated blood within 2 months of Visit 1 (Screening) or was planning to donate blood during the study
Had received any investigational drug within one month (or seven half-lives of the investigational drug, whichever was greater) of Visit 1 (Screening)
Had known allergies or hypersensitivity to any component of study treatment
Was employed by Elcelyx Therapeutics, Inc (that is an employee, temporary contract worker, or designee of the company)

About this study

Official title: A Randomized, Crossover Study Assessing the Single Dose Pharmacokinetics of Delayed-Release Metformin in Subjects With Renal Dysfunction

This study evaluated how a single dose of delayed-release metformin (Met DR) behaves in subjects with normal kidney function, mild kidney dysfunction, moderate kidney dysfunction, or severe kidney dysfunction. The safety and tolerability of Met DR was also examined. In addition, this study compared the behavior of a single dose of Met DR with that of extended-release metformin (Met XR) and placebo in subjects with the varying levels of kidney function described above.

Conditions: Renal Insufficiency
Being tested: Met DR, Met XR, Placebo
Medical subject headings: Renal Insufficiency

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

Study groups in NCT01658514
Study group	Role	What they receive
Met DR	Experimental	One dose of 1000 mg metformin delayed-release Receives: Drug: Met DR
Met XR	Active comparator	One dose of 1000 mg metformin extended-release Receives: Drug: Met XR
Placebo	Placebo comparator	One dose of Placebo Receives: Drug: Placebo

What is being measured

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

AUC (0-t) of Plasma Metformin
AUC (0-t) = Area under the curve from the time of dosing (0 h) to the time of the last quantifiable concentration following dose administration
Measured: from the time of dosing (0 h) to 72 hours postdose
Cmax of Plasma Metformin
Cmax = Maximum concentration from the time of dosing (0 h) to the time of the last quantifiable metformin concentration following dose administration
Measured: from the time of dosing (0 h) to 72 hours postdose
Correlation of Placebo-adjusted Change From Pre-dose Value in Lactate Versus Metformin Concentration
To determine the exposure-response relationship of metformin and plasma lactate concentrations
Measured: from the time of dosing (0 h) to 24 hours postdose

Timeline

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

Jan 2014Jun 2014

First posted7 Aug 2012 (estimated)
Study startJan 2014
Primary completionJun 2014
Study completionJun 2014

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 (2)Papers the sponsor has linked to this study.
Other trials for Renal InsufficiencyStudies 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: Basic science
Allocation: Randomised
Intervention model: Crossover
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 39 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01658514
Sponsor's protocol ID: LCRM101
Status last verified: Nov 2015
First submitted: 1 Aug 2012
Last updated: 30 Dec 2015
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Bakris GL, Mudaliar, S, Kim T, Burns C, Skare S, Baron A, Fineman M. Effects of New Metformin Formulation in Stage 3 and 4 CKD: A Pilot Study. J Am Soc Nephrol. 2014; 25:549A.
DeFronzo R, Fleming GA, Chen K, Bicsak TA. Metformin-associated lactic acidosis: Current perspectives on causes and risk. Metabolism. 2016 Feb;65(2):20-9. doi: 10.1016/j.metabol.2015.10.014. Epub 2015 Oct 9.
PubMed 26773926

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 Renal Insufficiency trials

Study at a glance

From the registry record, last updated by the sponsor on 30 Dec 2015. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomized, Crossover Study Assessing the Single Dose Pharmacokinetics of Delayed-Release Metformin in Subjects With Renal Dysfunction
ClinicalTrials.gov ID: NCT01658514
Acronym / sponsor ID: LCRM101
Conditions: Renal Insufficiency
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 39 participants (actual)
Lead sponsor: Elcelyx Therapeutics, Inc.Industry (pharma, biotech, devices)
Study start: Jan 2014
Primary completion: Jun 2014 (actual)
Study completion: Jun 2014 (actual)
First posted: 7 Aug 2012 (estimated)
Results: Posted 30 Dec 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: Basic science
Allocation: Randomised
Intervention model: Crossover
Masking: Double blind (participant, investigator)
Number of arms: 3

Arm	Type	Receives
Met DR	Experimental	Drug: Met DROne dose of 1000 mg metformin delayed-release
Met XR	Active comparator	Drug: Met XROne dose of 1000 mg metformin extended-release
Placebo	Placebo comparator	Drug: PlaceboOne dose of Placebo

Who may qualify

Ages: 18 to 80 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (11 listed)

18 to 80 (inclusive) years old at Visit 1 (Screening)
Male, or female and met all of the following criteria:
Body mass index (BMI) of 18.0 to 40.0 kg/m² (inclusive) at Visit 1 (Screening)
Had type 2 diabetes mellitus and an HbA1c ≤10.0%
Had a physical examination with no clinically significant abnormalities as judged by the investigator

Key exclusion criteria (30 listed)

Had End Stage Renal Disease requiring dialysis or severe renal dysfunction with eGFR <15 mL/min/1.73 m²
Was on dialysis or had been on dialysis within 12 months of Visit 1 (Screening)
Had received or planned to receive any iodinated contrast dye within 1 week prior to Visit 1 (Screening) or after study medication administration
Was taking or had taken within 1 week of Visit 1 cationic drugs that are eliminated by renal tubular secretion (e.g., amiloride, digoxin, morphine, procainamide, quinidine, quinine, ranitidine, triamterene, trimethoprim, and vancomycin)
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:

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	Met DR
Met XRmetformin extended-release tablets	Drug	Met XR
Placebo	Drug	Placebo

Primary outcome

AUC (0-t) of Plasma Metformin
Time frame: from the time of dosing (0 h) to 72 hours postdose
AUC (0-t) = Area under the curve from the time of dosing (0 h) to the time of the last quantifiable concentration following dose administration
Cmax of Plasma Metformin
Time frame: from the time of dosing (0 h) to 72 hours postdose
Cmax = Maximum concentration from the time of dosing (0 h) to the time of the last quantifiable metformin concentration following dose administration
Correlation of Placebo-adjusted Change From Pre-dose Value in Lactate Versus Metformin Concentration
Time frame: from the time of dosing (0 h) to 24 hours postdose
To determine the exposure-response relationship of metformin and plasma lactate concentrations

Results and safety

Results posted to the registry on 30 Dec 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
Sequence ABC	14	13
Sequence CAB	11	11
Sequence BCA	14	12

Primary outcome: AUC (0-t) of Plasma Metformin

Time frame: from the time of dosing (0 h) to 72 hours postdose. Least squares mean (Standard Error). Unit: ng*h/mL

Measure	Met DR n = 34	Met XR n = 34
Normal (N = 8)	5362 (943)	10411 (1831)
Mild RI (N = 10)	8705 (1368)	11788 (1853)
Moderate RI (N = 9)	11477 (1915)	20240 (3377)
Severe RI (N = 7)	22893 (4307)	43683 (8218)

Met DR vs Met XR: % Ratio of LS Means: 51.5 (90% CI 37.77 to 70.23), p = 0.0011, ANOVA
Met DR vs Met XR: % Ratio of LS Means: 73.8 (90% CI 55.97 to 97.43), p = 0.0733, ANOVA
Met DR vs Met XR: % Ratio of LS Means: 56.7 (90% CI 42.25 to 76.10), p = 0.0028, ANOVA

Population analysed: PK Evaluable Population

Primary outcome: Cmax of Plasma Metformin

Time frame: from the time of dosing (0 h) to 72 hours postdose. Least squares mean (Standard Error). Unit: ng/mL

Measure	Met DR n = 34	Met XR n = 34
Normal (N = 8)	969 (153)	1479 (234)
Mild RI (N = 10)	1036 (147)	1340 (189)
Moderate RI (N = 9)	925 (139)	1634 (245)
Severe RI (N = 7)	1414 (239)	2590 (438)

Met DR vs Met XR: % Ratio of LS Means: 65.5 (90% CI 46.32 to 92.68), p = 0.0474, ANOVA
Met DR vs Met XR: % Ratio of LS Means: 77.3 (90% CI 56.72 to 105.41), p = 0.1691, ANOVA
Met DR vs Met XR: % Ratio of LS Means: 56.6 (90% CI 40.73 to 78.63), p = 0.0064, ANOVA

Population analysed: PK Evaluable Population

Primary outcome: Correlation of Placebo-adjusted Change From Pre-dose Value in Lactate Versus Metformin Concentration

Time frame: from the time of dosing (0 h) to 24 hours postdose. Number. Unit: R²

Measure	Met DR n = 34	Met XR n = 34
Value	0.000011129	0.069527

Met DR: p = 0.9444, Pearson Correlation
Met XR: p <0.0001, Pearson Correlation

Population analysed: PD Evaluable Population

Adverse events

Time frame: Approximately 19 to 76 days depending on the number of days before the start of Visits 2 and 3 and the number of washout days between the treatment visits.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Placebo	0 of 36 (0%)	4 of 36 (11.1%)	Not reported
Met DR	0 of 38 (0%)	12 of 38 (31.6%)	Not reported
Met XR	0 of 37 (0%)	11 of 37 (29.7%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 30 Dec 2015.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publicationBakris GL, Mudaliar, S, Kim T, Burns C, Skare S, Baron A, Fineman M. Effects of New Metformin Formulation in Stage 3 and 4 CKD: A Pilot Study. J Am Soc Nephrol. 2014; 25:549A.
Results publication: PubMed 26773926DeFronzo R, Fleming GA, Chen K, Bicsak TA. Metformin-associated lactic acidosis: Current perspectives on causes and risk. Metabolism. 2016 Feb;65(2):20-9. doi: 10.1016/j.metabol.2015.10.014. Epub 2015 Oct 9.

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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.

George Canas, MD principal investigator

Prism Research

Kenneth Lasseter, MD principal investigator

Clinical Pharmacology of Miami, Inc

Alexander White, MD principal investigator

Progressive Medical Research

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Met DR and Met XR in people with Renal Insufficiency, 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 11 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 30 Dec 2015. 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 30 Dec 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?

AUC (0-t) of Plasma Metformin (time frame: from the time of dosing (0 h) to 72 hours postdose). The study lists 3 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 NCT01658514, which also lists 2 linked publications.

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 30 Dec 2015.