Type 1 Diabetes MellitusPhase 1NCT02059174
A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of MK-1293 Compared With a Basal Insulin in Participants With Type 1 Diabetes (MK-1293-005)
A Phase 1 study testing MK-1293, EU-Lantus™ and Novolog™ in people with Type 1 Diabetes Mellitus, run by Merck Sharp & Dohme LLC.
Trial summary
The purpose of this study is to assess the safety, pharmacokinetics, and pharmacodynamics of MK-1293 compared with a basal insulin (EU-Lantus™) in participants with Type 1 Diabetes. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Type 1 Diabetes Mellitus
- What is being tested?
- MK-1293, EU-Lantus™ and Novolog™
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 76 participants
- Where
- No sites listed yet
- Study dates
- 10 Feb 2014to 27 Apr 2015
- Phase
- Phase 1
- 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
- Has type 1 diabetes mellitus diagnosed at least 12 months before screening
- Subject to investigator discretion, is on a stable dose of insulin for at least 2 weeks before screening
- Has a total daily insulin dose <=1.2 units/kg
- Has a screening hemoglobin A1c <9.5%
- Has a body mass index >18.0 and <=30.0 kg/m^2
- Has a weight >=50 kg
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- Female participant of reproductive potential has a serum beta-human chorionic gonadotropin level consistent with the nongravid state and agrees to use (and/or have her partner use) 2 acceptable methods of birth control until 2 weeks after the last dose of study drug
- Postmenopausal female participant is without menses for >=1 year
- Surgically sterile female participant status is post hysterectomy, oophorectomy, or tubal ligation
- Has not used nicotine or nicotine-containing products for at least 3 months before study start or smokes less than 10 cigarettes per day and is willing to abstain during the trial
Who cannot join
- Has a history of clinically significant gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary, or major neurological abnormalities or disease
- Has a history of clinically significant endocrine abnormalities or diseases except type 1 diabetes mellitus
- Has had any severe hypoglycemic episodes associated with hypoglycemic seizures, comas, or unconsciousness within the past 3 months
- Has a history of diabetic ketoacidosis within the past 6 months
- Has a history of significant multiple or severe allergies, anaphylactic reaction, or significant intolerability to drugs or food
- Has a history of hypersensitivity to pharmacologic insulins
Show all 16Show fewer
- Is positive for hepatitis B surface antigen, hepatitis C, or Human Immunodeficiency Virus
- Has had major surgery or donated or lost 1 unit of blood within 4 weeks before screening
- Unable to refrain from use of any medication or herbal remedy from 2 weeks prior to the first dose of study drug to until the posttrial visit. Some medications are permitted and may be discussed with the investigators
- Vaccination within 12 weeks of start of study participation
- Consumes >3 glasses of alcoholic beverages per day. Participants consuming 4 glasses of alcoholic beverages may be enrolled at the discretion of the investigator.
- Consumes >6 servings of caffeinated beverages per day
- Is a regular user of any illicit drugs or has a history of drug abuse (including alcohol) within approximately 1 year
- Is on a carbohydrate-restricted diet (<100 grams carbohydrate per day); participants who are on a carbohydrate-restricted diet may be included if they agree to a diet consisting of >=100 grams of carbohydrate daily throughout the study
- Has a personal or family history of hypercoagulability or thromboembolic disease
- Has used systemic glucocorticoids within 3 months of screening or anticipates treatment with systemic glucocorticoids during study participation.
About this study
Official title: A Single Dose Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of MK-1293 and to Compare Its Pharmacologic Properties to Those of Another Basal Insulin in Subjects With Type I Diabetes
The purpose of this study is to assess the safety, pharmacokinetics, and pharmacodynamics of MK-1293 compared with a basal insulin (EU-Lantus™) in participants with Type 1 Diabetes. The primary hypotheses are that the duration of action, pharmacodynamic profile, and pharmacokinetic profile of MK-1293 and the comparator basal insulin are similar.
- Conditions
- Type 1 Diabetes Mellitus
- Being tested
- MK-1293, EU-Lantus™, Novolog™
- Medical subject headings
- Diabetes Mellitus, Type 1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MK-1293Drug
MK-1293 0.4 units/kg administered subcutaneously
EU-Lantus™Drug
EU-Lantus™ 0.4 units/kg administered subcutaneously
Novolog™Drug
Participants will receive an intravenous infusion of insulin aspart (Novolog™ or other rapid-acting insulin analog) for several hours prior to MK-1293 or EU-Lantus™ dosing in each dosing period to meet basal insulin requirements
| Study group | Role | What they receive |
|---|---|---|
| MK-1293 / EU-Lantus™ / MK-1293 / EU-Lantus™ | Experimental | MK-1293 or EU-Lantus™ 0.4 units/kg administered subcutaneously on Day 1 in 2 out of 4 study periods in a replicate crossover design with a minimum of 7 days between each treatment period Receives: Drug: MK-1293; Drug: EU-Lantus™; Drug: Novolog™ |
| EU-Lantus™ / MK-1293 / EU-Lantus™ / MK-1293 | Experimental | MK-1293 or EU-Lantus™ 0.4 units/kg administered subcutaneously on Day 1 in 2 out of 4 study periods in a replicate crossover design with a minimum of 7 days between each treatment period Receives: Drug: MK-1293; Drug: EU-Lantus™; Drug: Novolog™ |
What is being measured
The primary outcome is the main question the study is designed to answer.
Comparison of MK-1293 and EU-Approved Lantus Duration of Pharmacodynamic Action During a 30-Hour Euglycemic Clamp Study
Duration of Action (DOA) is defined as the length of time from dosing to End of Action. End of Action is defined as the time point at which plasma glucose has been above 150 mg/dL for 30 minutes and no glucose has been infused for 30 minutes. Median and max below are reported for the length of clamp duration (i.e. 30 hours).
Measured: Up to 30 hours postdose
PD: Area Under the Glucose Infusion Rate Versus Time Curve Over 24 Hours After Dosing (GIR-AUC0-24hr)
The area under the glucose infusion rate curve from hours 0 to 24 after injection (AUC[GIR{0-24}]) for participants who received either MK-1293 or EU-Lantus™ administered subcutaneously on Day 1 in 2 out of 4 study periods in a replicate crossover design was measured from blood samples obtained during a euglycemic clamp procedure.
Measured: Up to 24 hours postdose
PD: Area Under the Glucose Infusion Rate Versus Time Curve Over the First 12 Hours After Dosing (GIR-AUC0-12hr)
The area under the glucose infusion rate curve from hours 0 to 12 after injection (AUC[GIR{0-12}]) for participants who received either MK-1293 or EU-Lantus™ administered subcutaneously on Day 1 in 2 out of 4 study periods in a replicate crossover design was measured from blood samples obtained during a euglycemic clamp procedure.
Measured: Up to 12 hours postdose
PD: Area Under the Glucose Infusion Rate Versus Time Curve Over the Second 12 Hours After Dosing (GIR-AUC12-24hr)
The area under the glucose infusion rate curve from hours 12 to 24 after injection (AUC[GIR{12-24}]) for participants who received either MK-1293 or Lantus™ administered subcutaneously on Day 1 in 2 out of 4 study periods in a replicate crossover design was measured from blood samples obtained during a euglycemic clamp procedure.
Measured: From 12 to 24 hours postdose
PD: Maximum Glucose Infusion Rate (GIRmax)
Maximum glucose infusion rate (GIR[max]) based on smoothed data for participants who received either MK-1293 or EU-Lantus™ administered subcutaneously on Day 1 in 2 out of 4 study periods in a replicate crossover design was measured from blood samples obtained during a euglycemic clamp procedure.
Measured: Up to 30 hours postdose
M1 Glargine Metabolite Pharmacokinetics (PK): Area Under the Plasma Concentration Versus Time Curve (AUC0-24)
M1 glargine is the dominant circulating glargine-derived insulin metabolite after subcutaneous injection and it is pharmacologically active. AUC0-24 is a measure of the total amount of drug in the plasma from the dose to Hour 24. Analysis was performed on log scale with results back transformed to the original scale
Measured: Up to 24 hours postdose
M1 Glargine Metabolite PK: Maximum Plasma Concentration (Cmax)
M1 glargine is the dominant circulating glargine-derived insulin metabolite after subcutaneous injection and it is pharmacologically active. Cmax is a measure of the maximum amount of drug in the plasma after the dose is given. Analysis was performed on log scale with results back transformed to original scale.
Measured: Up to 24 hours postdose
Secondary outcomes (2)
M1 Glargine Metabolite PK: Area Under the Plasma Concentration Versus Time Curve Over the First 12 Hours After Dosing (AUC0-12)
M1 glargine is the dominant circulating glargine-derived insulin metabolite after subcutaneous injection and it is pharmacologically active. AUC0-12 is a measure of the total amount of drug in the plasma from the dose to Hour 12. Analysis was performed on log scale with results back transformed to original scale.
Measured: Up to 12 hours postdose
M1 Glargine Metabolite PK: Area Under the Plasma Concentration Versus Time Curve Over the Second 12 Hours After Dosing (AUC12-24)
M1 glargine is the dominant circulating glargine-derived insulin metabolite after subcutaneous injection and it is pharmacologically active. AUC12-24 is a measure of the total amount of drug in the plasma from Hour 12 to Hour 24. Analysis was performed on log scale with results back transformed to original scale.
Measured: From 12 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.
- First posted11 Feb 2014 (estimated)
- Study start10 Feb 2014
- Primary completion30 Mar 2015
- Study completion27 Apr 2015
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 1 Diabetes MellitusStudies of the same condition, open and under way.
- More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
- 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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 76 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck Sharp & Dohme LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Merck Sharp & Dohme LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02059174
- Sponsor's protocol ID
- 1293-005
- Other IDs
- 2012-005656-41
- Status last verified
- Aug 2018
- First submitted
- 7 Feb 2014
- Last updated
- 5 Sep 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Yes: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
Publications
Crutchlow MF, Palcza JS, Mostoller KM, Mahon CD, Barbour AM, Marcos MC, Xu Y, Watkins E, Morrow L, Hompesch M. Single-dose euglycaemic clamp studies demonstrating pharmacokinetic and pharmacodynamic similarity between MK-1293 insulin glargine and originator insulin glargine (Lantus) in subjects with type 1 diabetes and healthy subjects. Diabetes Obes Metab. 2018 Feb;20(2):400-408. doi: 10.1111/dom.13084. Epub 2017 Sep 26.
PubMed 28817223
Study at a glance
From the registry record, last updated by the sponsor on 5 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single Dose Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of MK-1293 and to Compare Its Pharmacologic Properties to Those of Another Basal Insulin in Subjects With Type I Diabetes
- ClinicalTrials.gov ID
- NCT02059174
- Acronym / sponsor ID
- 1293-005
- Conditions
- Type 1 Diabetes Mellitus
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 76 participants (actual)
- Lead sponsor
- Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
- Study start
- 10 Feb 2014 (actual)
- Primary completion
- 30 Mar 2015 (actual)
- Study completion
- 27 Apr 2015 (actual)
- First posted
- 11 Feb 2014 (estimated)
- Results
- Posted 8 Mar 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to assess the safety, pharmacokinetics, and pharmacodynamics of MK-1293 compared with a basal insulin (EU-Lantus™) in participants with Type 1 Diabetes. The primary hypotheses are that the duration of action, pharmacodynamic profile, and pharmacokinetic profile of MK-1293 and the comparator basal insulin are similar.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| MK-1293 / EU-Lantus™ / MK-1293 / EU-Lantus™ | Experimental | Drug: MK-1293, Drug: EU-Lantus™, Drug: Novolog™MK-1293 or EU-Lantus™ 0.4 units/kg administered subcutaneously on Day 1 in 2 out of 4 study periods in a replicate crossover design with a minimum of 7 days between each treatment period |
| EU-Lantus™ / MK-1293 / EU-Lantus™ / MK-1293 | Experimental | Drug: MK-1293, Drug: EU-Lantus™, Drug: Novolog™MK-1293 or EU-Lantus™ 0.4 units/kg administered subcutaneously on Day 1 in 2 out of 4 study periods in a replicate crossover design with a minimum of 7 days between each treatment period |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Has type 1 diabetes mellitus diagnosed at least 12 months before screening
- Subject to investigator discretion, is on a stable dose of insulin for at least 2 weeks before screening
- Has a total daily insulin dose <=1.2 units/kg
- Has a screening hemoglobin A1c <9.5%
- Has a body mass index >18.0 and <=30.0 kg/m^2
Key exclusion criteria (16 listed)
- Has a history of clinically significant gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary, or major neurological abnormalities or disease
- Has a history of clinically significant endocrine abnormalities or diseases except type 1 diabetes mellitus
- Has had any severe hypoglycemic episodes associated with hypoglycemic seizures, comas, or unconsciousness within the past 3 months
- Has a history of diabetic ketoacidosis within the past 6 months
- Has a history of significant multiple or severe allergies, anaphylactic reaction, or significant intolerability to drugs or food
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 |
|---|---|---|
| MK-1293MK-1293 0.4 units/kg administered subcutaneously | Drug | EU-Lantus™ / MK-1293 / EU-Lantus™ / MK-1293, MK-1293 / EU-Lantus™ / MK-1293 / EU-Lantus™ |
| EU-Lantus™EU-Lantus™ 0.4 units/kg administered subcutaneously | Drug | EU-Lantus™ / MK-1293 / EU-Lantus™ / MK-1293, MK-1293 / EU-Lantus™ / MK-1293 / EU-Lantus™ |
| Novolog™Participants will receive an intravenous infusion of insulin aspart (Novolog™ or other rapid-acting insulin analog) for several hours prior to MK-1293 or EU-Lantus™ dosing in each dosing period to meet basal insulin requirements | Drug | EU-Lantus™ / MK-1293 / EU-Lantus™ / MK-1293, MK-1293 / EU-Lantus™ / MK-1293 / EU-Lantus™ |
Primary outcome
Comparison of MK-1293 and EU-Approved Lantus Duration of Pharmacodynamic Action During a 30-Hour Euglycemic Clamp Study
Time frame: Up to 30 hours postdose
Duration of Action (DOA) is defined as the length of time from dosing to End of Action. End of Action is defined as the time point at which plasma glucose has been above 150 mg/dL for 30 minutes and no glucose has been infused for 30 minutes. Median and max below are reported for the length of clamp duration (i.e. 30 hours).
PD: Area Under the Glucose Infusion Rate Versus Time Curve Over 24 Hours After Dosing (GIR-AUC0-24hr)
Time frame: Up to 24 hours postdose
The area under the glucose infusion rate curve from hours 0 to 24 after injection (AUC[GIR{0-24}]) for participants who received either MK-1293 or EU-Lantus™ administered subcutaneously on Day 1 in 2 out of 4 study periods in a replicate crossover design was measured from blood samples obtained during a euglycemic clamp procedure.
PD: Area Under the Glucose Infusion Rate Versus Time Curve Over the First 12 Hours After Dosing (GIR-AUC0-12hr)
Time frame: Up to 12 hours postdose
The area under the glucose infusion rate curve from hours 0 to 12 after injection (AUC[GIR{0-12}]) for participants who received either MK-1293 or EU-Lantus™ administered subcutaneously on Day 1 in 2 out of 4 study periods in a replicate crossover design was measured from blood samples obtained during a euglycemic clamp procedure.
PD: Area Under the Glucose Infusion Rate Versus Time Curve Over the Second 12 Hours After Dosing (GIR-AUC12-24hr)
Time frame: From 12 to 24 hours postdose
The area under the glucose infusion rate curve from hours 12 to 24 after injection (AUC[GIR{12-24}]) for participants who received either MK-1293 or Lantus™ administered subcutaneously on Day 1 in 2 out of 4 study periods in a replicate crossover design was measured from blood samples obtained during a euglycemic clamp procedure.
PD: Maximum Glucose Infusion Rate (GIRmax)
Time frame: Up to 30 hours postdose
Maximum glucose infusion rate (GIR[max]) based on smoothed data for participants who received either MK-1293 or EU-Lantus™ administered subcutaneously on Day 1 in 2 out of 4 study periods in a replicate crossover design was measured from blood samples obtained during a euglycemic clamp procedure.
M1 Glargine Metabolite Pharmacokinetics (PK): Area Under the Plasma Concentration Versus Time Curve (AUC0-24)
Time frame: Up to 24 hours postdose
M1 glargine is the dominant circulating glargine-derived insulin metabolite after subcutaneous injection and it is pharmacologically active. AUC0-24 is a measure of the total amount of drug in the plasma from the dose to Hour 24. Analysis was performed on log scale with results back transformed to the original scale
M1 Glargine Metabolite PK: Maximum Plasma Concentration (Cmax)
Time frame: Up to 24 hours postdose
M1 glargine is the dominant circulating glargine-derived insulin metabolite after subcutaneous injection and it is pharmacologically active. Cmax is a measure of the maximum amount of drug in the plasma after the dose is given. Analysis was performed on log scale with results back transformed to original scale.
2 secondary outcomes
M1 Glargine Metabolite PK: Area Under the Plasma Concentration Versus Time Curve Over the First 12 Hours After Dosing (AUC0-12)
Time frame: Up to 12 hours postdose
M1 Glargine Metabolite PK: Area Under the Plasma Concentration Versus Time Curve Over the Second 12 Hours After Dosing (AUC12-24)
Time frame: From 12 to 24 hours postdose
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Sep 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 28817223Crutchlow MF, Palcza JS, Mostoller KM, Mahon CD, Barbour AM, Marcos MC, Xu Y, Watkins E, Morrow L, Hompesch M. Single-dose euglycaemic clamp studies demonstrating pharmacokinetic and pharmacodynamic similarity between MK-1293 insulin glargine and originator insulin glargine (Lantus) in subjects with type 1 diabetes and healthy subjects. Diabetes Obes Metab. 2018 Feb;20(2):400-408. doi: 10.1111/dom.13084. Epub 2017 Sep 26.
- Individual participant dataSharing planned: Yes. https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
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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.
Medical Director study director
Merck Sharp & Dohme LLC
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing MK-1293, EU-Lantus™ and Novolog™ in people with Type 1 Diabetes Mellitus, run by Merck Sharp & Dohme LLC.
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 10 inclusion and 16 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 5 Sep 2018. 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. 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 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.
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 8 Mar 2017). 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?
Comparison of MK-1293 and EU-Approved Lantus Duration of Pharmacodynamic Action During a 30-Hour Euglycemic Clamp Study (time frame: Up to 30 hours postdose). The study lists 7 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 NCT02059174, 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 5 Sep 2018.