Phase 1
N=33
Multiple Ascending Dose Study of MK-5160 in Participants With Type 1 and Type 2 Diabetes Mellitus (MK-5160-002)
Type 1 Diabetes Mellitus · Type 2 Diabetes Mellitus
Bottom Line
View on ClinicalTrials.gov: NCT03095651 ↗Enrolled (actual)
33
Serious AEs
0.0%
Results posted
Apr 2019
Primary outcome: Primary: Number of Participants Experiencing an Adverse Event (AE) — 6; 6; 0; 4 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- MK-5160 16 nmol/kg (Biological); MK-5160 32 nmol/kg (Biological); MK-5160 64 nmol/kg (Biological); Glargine 0.4 U/kg (Biological); Placebo to Glargine (Biological); Placebo to MK-5160 (Biological); Dextrose (Drug); Glargine 0.6 U/kg (Biological)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Merck Sharp & Dohme LLC
- Primary completion
- Jan 2018
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants Experiencing an Adverse Event (AE) |
6; 6; 0; 4; 0; 7 | — |
| PRIMARY Number of Participants Discontinuing Study Drug Due to an AE |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Maximal Glucose Infusion Rate |
2.15; 2.86; 2.56; 1.98; 2.15; 3.25 | — |
| SECONDARY Maximum Plasma Concentration (Cmax) of MK-5160 |
0.76; 1.58; 1.33; 1.91; 2.33; 5.38 | — |
| SECONDARY Maximum Plasma Concentration (Cmax) of Glargine |
17.26; 18.97; 20.28; 34.18 | — |
| SECONDARY Day 12 to Day 1 Accumulation Ratio of Cmax |
3.08; 3.40; 1.17; 2.89; 4.72; 1.80 | — |
| SECONDARY Steady State Plasma Concentration (Css) of MK-5160 |
1.79; 4.40; 2.64; 6.15 | — |
| SECONDARY Steady State Plasma Concentration (Css) of Glargine |
9.99; 14.72 | — |
| SECONDARY Plasma Concentration/Time (AUC0-24) of MK-5160 |
9.79; 26.39; 17.44; 25.32; 42.90; 105.5 | — |
| SECONDARY Plasma Concentration/Time (AUC0-24) of Glargine |
193.6; 149.6; 239.8; 353.3 | — |
| SECONDARY Day 12 to Day 1 Accumulation Ratio of AUC0-24. |
4.38; 4.00; 1.24; 3.63; 5.83; 2.36 | — |
| SECONDARY Plasma Clearance |
0.37; 0.30; 10.01; 0.51; 0.43; 10.19 | — |
| SECONDARY Time to Maximum Plasma Concentration |
0.75; 0.75; 3.49; 1.00; 1.00; 1.49 | — |
| SECONDARY Apparent Terminal Half-life |
20.01; 21.69; 13.10; 14.47 | — |
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.
Eligibility Criteria
Inclusion Criteria
- 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:
- Be on no anti-hyperglycemic agent (AHA), or on metformin monotherapy or metformin plus a dipeptidyl peptidase-4 (DPP4) inhibitor at stable doses for at least 8 weeks prior to screening, with a screening HbA1C ≥7.0 and ≤10.0%.
- Be on either a sulfonylurea (e.g. glyburide) or an alpha-glucosidase inhibitors (e.g., acarbose) alone or in combination with metformin at stable doses for at least 8 weeks prior to screening with a screening HbA1C ≥7.0 and ≤9.0%. Participants on these medications must be willing to stop the sulfonylurea or alpha-glucosidase inhibitor after screening once they qualify for study participation.
- Have a BMI ≥18.5 kg/m^2 and ≤ 35.0 kg/m^2 BMI = mass (kg)/height (m)^2
- May be on selected standard medications for T2DM, including alpha-glucosidase inhibitors (e.g., acarbose), sulfonylureas (e.g. glyburide), DPP-4 inhibitors, and metformin. Participants on alpha-glucosidase inhibitors and/or sulfonylureas must stop these medications for at least one week prior to checking into the site and for the duration of the trial through the last dose of MK-5160/glargine. Participants on metformin or DPP-4 inhibitors may continue on their home dose for the duration of the trial. Participants on SGLT2 inhibitors (gliflozins), thiazolidinediones or GLP-1 agonists are excluded.
- Be a nonsmoker or smoker who uses no greater than 5 cigarettes or equivalent (e.g., e-cigarettes) daily over the prior 3 month period. Participants must agree to follow the smoking restrictions defined by the CRU.
Exclusion Criteria
- 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 t
Data sourced from ClinicalTrials.gov (NCT03095651). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.