Single Ascending Dose Study of MK-1092 in Healthy Participants and in Participants With Type 1 and Type 2 Diabetes Mellitus (MK-1092-001)
A Single Ascending Dose Clinical Trial to Study the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of MK-1092 in Healthy Subjects, Subjects With Type 1 Diabetes Mellitus, and Subjects With Type 2 Diabetes Mellitus.
2 other identifiers
interventional
69
1 country
1
Brief Summary
This is an active- and placebo-controlled, single-site, four-part trial of MK-1092 in healthy adult participants, in participants with type 1 diabetes mellitus (T1DM), and in participants with type 2 diabetes mellitus (T2DM). The primary hypothesis for this study is that at a dose with sufficient safety, the mean maximal glucose infusion rate (GIRmax) after single subcutaneous (SC) administration of MK-1092 in adult participants with T1DM is within an acceptable range. (Part 3)
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Aug 2017
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 26, 2017
CompletedFirst Posted
Study publicly available on registry
May 31, 2017
CompletedStudy Start
First participant enrolled
August 16, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 8, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
November 8, 2018
CompletedResults Posted
Study results publicly available
November 15, 2019
CompletedNovember 15, 2019
November 1, 2019
1.2 years
May 26, 2017
October 10, 2019
November 14, 2019
Conditions
Outcome Measures
Primary Outcomes (3)
Number of Participants Who Experienced an Adverse Event (AE)
An adverse event is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study. Adverse events that occurred beyond 14 days of dosing were considered Post-Trial AEs. Given the half-life of MK-1092 and glargine, any events observed beyond 14 days would not be considered a result of study drug and were therefore presented together.
Up to 112 days
Number of Participants Who Discontinued the Study Due to an AE
An adverse event is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study. Adverse events that occurred beyond 14 days of dosing were considered Post-Trial AEs. Given the half-life of MK-1092 and glargine, any events observed beyond 14 days would not be considered a result of study drug and were therefore presented together.
Up to 58 days
GIRmax After a Single Dose Administration of Subcutaneous MK-1092 or Glargine to Adult Participants With Type 1 Diabetes Mellitus (T1DM) (Part 3)
The GIRmax required to maintain blood glucose at each participants' individual clamp target, following administration of MK-1092 SC or glargine SC was determined by use of a continuous glucose infusion during the euglycemic clamp so that glucose levels remained in the euglycemic range and hypoglycemia was prevented. Blood glucose was monitored frequently (\~every 5 minutes), allowing rapid changes to the rate of glucose infusion. Mean and 95% CI were based on a linear fixed effects model containing a fixed effect for treatment (MK-1092 Doses, Glargine). In Part 3, 4 participants (across 2 dosing panels) received glargine. These 4 participants were analyzed together given the small numbers and the same treatment (same dose of glargine) received.
Up to approximately 24 hours post-dose
Secondary Outcomes (23)
GIRmax After a Single Dose Administration of Subcutaneous MK-1092 or Glargine to Healthy Adult Participants (Part 1)
Up to approximately 24 hours post-dose
GIRmax After a Single Dose Administration of Subcutaneous MK-1092 or Glargine to Adult Participants With Type 2 Diabetes Mellitus (T2DM) (Part 4)
Up to approximately 24 hours post-dose
Time-Weighted Average GIR (TWA[GIR]) After a Single Dose Administration of Subcutaneous MK-1092 or Glargine to Healthy Adult Participants (Part 1)
Up to approximately 24 hours post-dose
Time-Weighted Average GIR (TWA[GIR]) After a Single Dose Administration of Subcutaneous MK-1092 or Glargine to Adult Participants With T1DM (Part 3)
Up to approximately 24 hours post-dose
Time-Weighted Average GIR (TWA[GIR]) After a Single Dose Administration of Subcutaneous MK-1092 or Glargine to Adult Participants With T2DM (Part 4)
Up to approximately 24 hours post-dose
- +18 more secondary outcomes
Study Arms (14)
Part 1, MK-1092, 4.0 nmol/kg
EXPERIMENTALMK-1092, 4.0 nmol/kg, SC, as a single dose under the euglycemic clamp, in healthy participants
Part 1, MK-1092, 8.0 nmol/kg
EXPERIMENTALMK-1092, 8.0 nmol/kg, SC, as a single dose under the euglycemic clamp, in healthy participants
Part 1, MK-1092, 16 nmol/kg
EXPERIMENTALMK-1092, 16 nmol/kg, SC, as a single dose under the euglycemic clamp, in healthy participants
Part 1, MK-1092, 32 nmol/kg
EXPERIMENTALMK-1092, 32 nmol/kg, SC, as a single dose under the euglycemic clamp, in healthy participants
Part 1, MK-1092, 64 nmol/kg
EXPERIMENTALMK-1092, 64 nmol/kg, SC, as a single dose under the euglycemic clamp, in healthy participants
Part 1, Glargine, 3.0 nmol/kg
ACTIVE COMPARATORGlargine, 3.0 nmol/kg, SC, as a single dose under the euglycemic clamp, in healthy participants
Part 2, MK-1092, 8.0 nmol/kg + lispro, 1.2 nmol/kg
EXPERIMENTALMK-1092, 8.0 nmol/kg dose selection based on Part 1 + lispro (Humalog®), 1.2 nmol/kg, as a single dose, in healthy participants
Part 3, MK-1092, 8.0 nmol/kg
EXPERIMENTALMK-1092, (8.0 nmol/kg based on Part 1), SC, in participants with T1DM.
Part 3, MK-1092, 32 nmol/kg
EXPERIMENTALMK-1092, 32 nmol/kg, SC, as a single dose, in participants with T1DM
Part 3, Glargine, 3.0 nmol/kg
ACTIVE COMPARATORGlargine, 3.0 nmol/kg, SC, as a single dose, in participants with T1DM
Part 4, MK-1092, 32 nmol/kg
EXPERIMENTALMK-1092, 32 nmol/kg, SC, as a single dose, in participants with T2DM
Part 4, MK-1092, 16 nmol/kg
EXPERIMENTALMK-1092, 16 nmol/kg, SC, as a single dose, in participants with T2DM
Part 4, MK-1092, 64 nmol/kg
EXPERIMENTALMK-1092, 64 nmol/kg, SC, as a single dose, in participants with T2DM
Part 4, Glargine, 3.0 nmol/kg
ACTIVE COMPARATORGlargine, 3.0 nmol/kg, SC, as a single dose, in participants with T2DM
Interventions
MK-1092, 4.0 nmol/kg, SC, as a single dose under the euglycemic clamp, in participants
MK-1092, 8.0 nmol/kg, SC, as a single dose under the euglycemic clamp, in participants
MK-1092, 16 nmol/kg, SC, as a single dose under the euglycemic clamp, in participants
MK-1092, 32 nmol/kg, SC, as a single dose under the euglycemic clamp, in participants
MK-1092, 64 nmol/kg, SC, as a single dose under the euglycemic clamp, in participants
Glargine 3.0 nmol/kg, SC, as a single dose
Lispro (Humalog®), 1.2 nmol/kg, IV infusion SC over 3 hours as a single dose starting \~12 hours after MK-1092 administration.
Placebo to glargine, SC, as a single dose
Placebo to MK-1092, SC, as a single dose
20% solution for continuous infusion for the duration of the glucose clamp as needed to maintain blood sugar at pre-clamp target levels.
Participants will receive insulin IV, as needed, prior to dosing and clamp initiation and after dosing.
Eligibility Criteria
You may qualify if:
- All participants
- Be a healthy male, or healthy female participant (excluding diabetes mellitus in Part 3 participants) of non-child bearing potential. A female non-child bearing potential is one who is postmenopausal without menses for at least 1 year or whose status is post hysterectomy, bilateral oophorectomy, or tubal ligation.
- Be judged to be in good health based on medical history, physical exam, vital sign measurements, electrocardiogram (ECG) and laboratory safety tests
- Have adequate venous access to support execution of trial procedures
- For Parts 1 and 2 (Healthy adult participants)
- Healthy male and female participants between the ages of 18 and 50 years (inclusive)
- Have a Body Mass Index (BMI) ≥18.5 kg/m\^2 and ≤28.0 kg/m\^2 at screening
- Have fasting blood glucose values at screening must be \<100 mg/dL
- Be a non-smoker and/or has not used nicotine or nicotine-containing products (e.g., nicotine patch) for at least approximately 3 months.
- For Part 3 (Adult participants with T1DM):
- Be male, or female of non-childbearing potential between 18 to 60 years of age
- Have a diagnosis of T1DM as defined by standard diagnostic criteria for ≥12 months at time of the pretrial (screening) visit
- Have a BMI ≥18.5 kg/m\^2 and ≤32 kg/m\^2 at screening.
- Be on stable doses of basal insulin over the 2-week period prior to screening and over the 2 weeks prior to dosing
- Have a total daily insulin requirement (basal plus prandial) of ≤1.2 units/kg at screening
- +9 more criteria
You may not qualify if:
- All participants
- Is mentally or legally incapacitated
- Has a history of clinically significant endocrine (excluding diabetes mellitus in Part 3 participants), gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary or major neurological (including stroke and chronic seizures) abnormalities or diseases.
- Has a systolic blood pressure (SBP) ≥140 mm Hg and/or a diastolic blood pressure (DBP) ≥90 mm Hg at screening.
- Is positive for hepatitis B surface antigen, hepatitis C antibodies or human immunodeficiency virus (HIV) at screening.
- Has a history of cancer (malignancy) Exceptions: (1) Participants with adequately treated non-melanomatous skin carcinoma or carcinoma in situ of the cervix may participate in the trial; (2) Participants with other malignancies which have been successfully treated ≥10 years prior to the pretrial (screening) visit
- Has a history of significant multiple and/or severe allergies (e.g. food, drug, latex allergy), or has had an anaphylactic reaction or significant intolerability (i.e. systemic allergic reaction) to prescription or non-prescription drugs or food.
- Had major surgery, donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks prior to the pretrial (screening) visit.
- Has participated in another investigational trial within 4 weeks.
- Has been randomized to, and received MK-5160 in prior clinical studies.
- Has a QTcF interval \>450 msec, has a history of risk factors for Torsades de Pointes (e.g., heart failure/cardiomyopathy or family history of Long QT Syndrome).
- Has uncorrected hypokalemia
- Has uncorrected hypomagnesemia
- Is taking concomitant medications that prolong the QT/QTc interval.
- Is unable to refrain from or anticipates the use of any medication, including prescription and non-prescription drugs or herbal remedies beginning approximately 2 weeks prior to administration of the initial dose of trial drug, throughout the trial, until the post-trial visit.
- +21 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
ProSciento Inc. ( Site 0001)
Chula Vista, California, 91911, United States
Related Publications (1)
Walford GA, Duncan KE, Hernandez M, Vaddady P, Hompesch M, Morrow L, Stoch SA. A Randomized, Single Ascending Dose Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of a Novel Insulin Dimer. Clin Pharmacol Ther. 2022 Jul;112(1):125-132. doi: 10.1002/cpt.2607. Epub 2022 May 3.
PMID: 35390172DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Senior Vice President, Global Clinical Development
- Organization
- Merck Sharp & Dohme Corp.
Study Officials
- STUDY DIRECTOR
Medical Director
Merck Sharp & Dohme LLC
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 26, 2017
First Posted
May 31, 2017
Study Start
August 16, 2017
Primary Completion
November 8, 2018
Study Completion
November 8, 2018
Last Updated
November 15, 2019
Results First Posted
November 15, 2019
Record last verified: 2019-11
Data Sharing
- IPD Sharing
- Will share
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf