Multiple Ascending Dose Study of MK-5160 in Participants With Type 1 and Type 2 Diabetes Mellitus (MK-5160-002)
A Study to Assess the Safety, Pharmacokinetics and Pharmacodynamic Effect of MK-5160 in Subjects With Type 1 and Type 2 Diabetes Mellitus
2 other identifiers
interventional
33
1 country
1
Brief Summary
This is a randomized, active- and placebo-controlled, double-blind trial of MK-5160 in participants with Type 1 diabetes mellitus (T1DM) and Type 2 diabetes mellitus (T2DM). This is a two-part trial, with three panels per part. T1DM (Part 1) and T2DM (Part 2) participants will be given daily fixed doses of MK-5160 in three predefined, increasing doses in each panel, or glargine (active comparator). The primary hypothesis of the trial is that at a dose with sufficient safety, the mean steady-state maximum level of glucose infusion rate (GIRmax) after MK-5160 administration in both T1DM and T2DM participants is between 1.5 and 4.5 mg/kg/min.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Apr 2017
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 27, 2017
CompletedFirst Posted
Study publicly available on registry
March 29, 2017
CompletedStudy Start
First participant enrolled
April 12, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 30, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
January 30, 2018
CompletedResults Posted
Study results publicly available
April 1, 2019
CompletedApril 1, 2019
March 1, 2019
10 months
March 27, 2017
December 14, 2018
March 29, 2019
Conditions
Outcome Measures
Primary Outcomes (3)
Number of Participants Experiencing an Adverse Event (AE)
An adverse event is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
Up to 33 days
Number of Participants Discontinuing Study Drug Due to an AE
An adverse event is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
Up to 12 days
Maximal Glucose Infusion Rate
Maximal glucose infusion rate required to maintain target glucose levels in a euglycemic clamp setting (GIRmax) at steady state (Day 12) following administration of study drug. In cases where the lower bound of the CI was negative, the lower confidence limit was truncated at zero. In these cases, the confidence intervals are 97.5% CIs.
Up to 24 hours post-dose on Day 12
Secondary Outcomes (11)
Maximum Plasma Concentration (Cmax) of MK-5160
Day 1 clamp: -15 min. (predose), 10, 30 min., 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours following start of injection (FSOI). Day 12: -15 min (predose), 10, 30 min., 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, and 168 hours FSOI.
Maximum Plasma Concentration (Cmax) of Glargine
Day 1 clamp: -15 min. (predose), 10, 30 min., 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours FSOI. Day 12: -15 min (predose), 10, 30 min., 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, and 168 hours FSOI.
Day 12 to Day 1 Accumulation Ratio of Cmax
Day 1 clamp: -15 min. (predose), 10, 30 min., 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours FSOI. Day 12: -15 min (predose), 10, 30 min., 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, and 168 hours FSOI.
Steady State Plasma Concentration (Css) of MK-5160
Day 12: -15 min (predose), 10, 30 min., 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, and 168 hours FSOI.
Steady State Plasma Concentration (Css) of Glargine
Day 12: -15 min (predose), 10, 30 min., 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, and 168 hours FSOI.
- +6 more secondary outcomes
Study Arms (8)
T1DM MK-5160 16 nmol/kg
EXPERIMENTALParticipants with T1DM received MK-5160, 16 nmol/kg, and placebo to glargine daily for 12 days. Dextrose was administered as needed to maintain blood sugar.
T1DM MK-5160 32 nmol/kg
EXPERIMENTALParticipants with T1DM received MK-5160, 32 nmol/kg, and placebo to glargine daily for 12 days. Dextrose was administered as needed to maintain blood sugar.
T1DM MK-5160 64 nmol/kg
EXPERIMENTALParticipants with T1DM received MK-5160 64 nmol/kg, and placebo to glargine daily for 12 days. Dextrose was administered as needed to maintain blood sugar.
T1DM Glargine 0.4 U/kg
ACTIVE COMPARATORParticipants with T1DM received Glargine 0.4 U/kg and placebo to MK-5160 daily for 12 days. Dextrose was administered as needed to maintain blood sugar.
T2DM MK-5160 16 nmol/kg
EXPERIMENTALParticipants with T2DM received MK-5160 16 nmol/kg, and placebo to glargine daily for 12 days. Dextrose was administered as needed to maintain blood sugar.
T2DM MK-5160 32 nmol/kg
EXPERIMENTALParticipants with T2DM received MK-5160 32 nmol/kg, and placebo to glargine daily for 12 days. Dextrose was administered as needed to maintain blood sugar.
T2DM MK-5160 64 nmol/kg
EXPERIMENTALParticipants with T2DM received MK-5160 64 nmol/kg, and placebo to glargine daily for 12 days. Dextrose was administered as needed to maintain blood sugar.
T2DM Glargine 0.6 U/kg
ACTIVE COMPARATORParticipants with T2DM received Glargine 0.6 U/kg and placebo to MK-5160 daily for 12 days. Dextrose was administered as needed to maintain blood sugar.
Interventions
MK-5160 16 nmol/kg, subcutaneous injection administered daily for 12 days
MK-5160 32 nmol/kg, subcutaneous injection administered daily for 12 days
MK-5160 64 nmol/kg, subcutaneous injection administered daily for 12 days
Glargine 0.4 U/kg, subcutaneous injection administered daily for 12 days
Placebo to glargine, subcutaneous injection administered daily for 12 days
Placebo to MK-5160, subcutaneous injection administered daily for 12 days
20% solution of dextrose; adjusted to maintain the various glycemic levels at 100 mg/dL given as a continuous intravenous infusion for 6-30 hours.
Glargine 0.6 U/kg, subcutaneous injection administered daily for 12 days
Eligibility Criteria
You may qualify if:
- For Part 1 (T1DM):
- Be male, or female of non-childbearing potential. A female of non-childbearing potential defined as a female who is postmenopausal without menses for at least 1 year and has a follicle stimulating hormone (FSH) value in the postmenopausal range upon pretrial (screening) evaluation OR a female who is status post hysterectomy, oophorectomy or tubal ligation.
- Be judged to be in good health
- Have a diagnosis of T1DM as defined by standard diagnostic criteria for ≥12 months at time study participation
- 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.
- Have a hemoglobin A1C (HbA1c) ≤10% at the time of study participation.
- Have a Body Mass Index (BMI) ≥18.5 kg/m\^2 and ≤ 32 kg/m\^2. BMI = mass (kg)/height (m)\^2
- Be a non-smoker or smoker who uses no more than 5 cigarettes or equivalent (e.g., e-cigarettes) per day over the prior 3 month period also may be enrolled (at the discretion of the investigator). The subject must agree to follow the smoking restrictions defined by the clinical research unit (CRU).
- For Part 2 (T2DM):
- Be male, or female of non-childbearing potential. A female of non-childbearing potential defined as a female who is postmenopausal without menses for at least 1 year and has a FSH value in the postmenopausal range upon pretrial (screening) evaluation OR a female who is status post hysterectomy, oophorectomy or tubal ligation.
- Be judged to be in good health
- Have a diagnosis of T2DM as defined by standard diagnostic criteria for ≥12 month at time of study participation.
- T2DM participants are not required to have been on insulin. If on insulin, participants should have a total daily insulin requirement of ≤ 1.2 units/kg, and have been on stable doses of basal insulin over the 2-week period prior to screening and over the 2 weeks prior to dosing.
- Meet one of the following criteria:
- +5 more criteria
You may not qualify if:
- For Part 1 (T1DM) and Part 2 (T2DM):
- Is under the age of legal consent
- Is mentally or legally incapacitated, has significant emotional problems at the time of pretrial (screening) visit or expected during the conduct of the trial or has a history of clinically significant psychiatric disorder of the last 5 years. Participants who have had situational depression may be enrolled in the trial at the discretion of the investigator.
- Has a history of clinically significant endocrine (excluding diabetes mellitus), gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary or major neurological (including stroke and chronic seizures) abnormalities or diseases. Participants with a history of uncomplicated kidney stones, as defined as spontaneous passage and no recurrence in the last 5 years, or childhood asthma may be enrolled in the trial at the discretion of the investigator.
- 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 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.
- Is positive for hepatitis B surface antigen, hepatitis C antibodies or HIV at Screening.
- Had major surgery, donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks prior to the pretrial visit.
- Has participated in another investigational trial within 4 weeks (or 5 half-lives), whichever is greater, prior to the pretrial visit.
- 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 (or 5 half-lives) prior to administration of the initial dose of trial drug, throughout the trial (including washout intervals between treatment periods), until the post-trial visit. Certain medications, such as antihypertensives and aspirin, are permitted.
- Consumes greater than 3 glasses of alcoholic beverages (1 glass is approximately equivalent to: beer \[354 mL/12 ounces\], wine \[118 mL/4 ounces\], or distilled spirits \[29.5 mL/1 ounce\]) per day.
- Consumes excessive amounts, defined as greater than 6 servings (1 serving is approximately equivalent to 120 mg of caffeine) of coffee, tea, cola, energy-drinks, or other caffeinated beverages per day.
- Is a regular user of cannabis or any illicit drugs, or has a history of drug (including alcohol) abuse within approximately 6 months.
- Has the diagnosis of hypoglycemia unawareness, or has had one or more severe hypoglycemic episodes associated with hypoglycemic seizures, comas or unconsciousness within 6 months prior to dosing.
- Has used systemic (intravenous, oral, inhaled) glucocorticoids within 3 months of screening or is anticipated to require treatment with systemic glucocorticoids during study participation.
- +7 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
ProSciento Inc. ( Site 0001)
Chula Vista, California, 91911, United States
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
March 27, 2017
First Posted
March 29, 2017
Study Start
April 12, 2017
Primary Completion
January 30, 2018
Study Completion
January 30, 2018
Last Updated
April 1, 2019
Results First Posted
April 1, 2019
Record last verified: 2019-03
Data Sharing
- IPD Sharing
- Will share
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf