Study of the Safety and Efficacy of MK-8521 Compared to Placebo and a Diabetes Drug in Participants With Type 2 Diabetes Mellitus (MK-8521-003)

NCT01982630 | Completed Phase 1 Results

• 1 other identifier: 8521-003
• Study Type: interventional
• Target: 87
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study will evaluate the safety, efficacy, and pharmacokinetics of MK-8521 given once daily compared to placebo and another diabetes drug in participants with Type 2 diabetes mellitus (T2DM). This study was modified by a protocol amendment to a 2-part trial to further test the safety and tolerability of MK-8521 at higher doses and to compare MK-8521 pharmacokinetics between participants with T2DM and healthy participants. An additional cohort of T2DM participants and a cohort of non-diabetic obese participants has been added.

Conditions

Diabetes Mellitus

Outcome Measures

Primary Outcomes (34)

• Number of Participants Experiencing Adverse Events (AEs) in Part 1

  An AE is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. AEs are presented by individual dose received by participants during titration in an assigned study treatment sequence.

  Up to approximately 42 days

• Number of Participants Experiencing Adverse Events (AEs) in Part 2

  An AE is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. AEs are presented by individual dose received by participants during titration in an assigned study treatment sequence.

  Up to approximately 57 days

• Number of Participants Discontinuing Study Drug Due to Adverse Events (AEs) in Part 1

  An AE is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. Discontinuations are presented by individual dose received by participants during titration in an assigned study treatment sequence.

  Up to approximately 14 days

• Number of Participants Discontinuing Study Drug Due to Adverse Events (AEs) in Part 2

  An AE is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. Discontinuations are presented by individual dose received by participants during titration in an assigned study treatment sequence.

  Up to approximately 29 days

• Change From Baseline in Time-weighted Average From 0 to 24 Hours (TWA0-24hr) of Heart Rate (HR) After 7 Days of Treatment in Type 2 Diabetes Mellitus (T2DM) Participants in Part 1

  Semi-recumbent heart rate was assessed at baseline on Day 1; Day 7 at predose, 2, 4, 6, 8, 12, 13, 14, 15, 16, 22 hours postdose; and prior to dosing on Day 8. Heart rate was measured in triplicate with at least a 1-2-minute interval between measurements. The repeated measurements were averaged before conducting the statistical analysis. TWA0-24hr was calculated as the area under the measurement-time curve (AUC) divided by the time period of over which the measurements were made (i.e. 24 hrs.). Change from baseline TWA0-24hr HR was calculated as the TWA0-24hr HR at Day 7 minus baseline where baseline was defined as predose on Day 1.

  Baseline (predose Day 1) and up to 24 hours post Day 7 dose

• Change From Baseline in Time-weighted Average From 0 to 24 Hours (TWA0-24hr) of Heart Rate (HR) After 7 Days of Treatment in Type 2 Diabetes Mellitus (T2DM) Participants in Part 2

  Semi-recumbent HR was measured in triplicate with at least a 1-2-minute interval between measurements at the following time points: baseline on Day 1; Day 7: predose, 2, 4, 6, 8, 12, and 16 hours postdose; and prior to dosing on Day 8. The repeated measurements were averaged before conducting the analysis. TWA0-24hr was calculated as the AUC divided by the time period of over which the measurements were made (i.e. 24 hrs.). Change from baseline TWA0-24hr HR was calculated as the TWA0-24hr HR at Day 7 minus baseline where baseline was defined as predose on Day 1.

  Baseline (predose Day 1) and up to 24 hours post Day 7 dose

• Change From Baseline in Time-weighted Average From 0 to 24 Hours (TWA0-24hr) of Heart Rate (HR) After 14 Days of Treatment in Type 2 Diabetes Mellitus (T2DM) Participants in Part 1

  Semi-recumbent HR was measured in triplicate with at least a 1-2-minute interval between measurements at the following time points: baseline on Day 1; Day 14: predose, 2, 4, 6, 8, 12, 13, 14, 15, 16, 22 hours postdose and prior to dosing on Day 15. The repeated measurements were averaged before conducting the analysis. TWA0-24hr was calculated as the AUC divided by the time period of over which the measurements were made (i.e. 24 hrs.). Change from baseline TWA0-24hr HR was calculated as the TWA0-24hr HR at Day 14 minus baseline where baseline was defined as predose on Day 1.

  Baseline (predose Day 1) and up to 24 hours post Day 14 dose

• Change From Baseline in Time-weighted Average From 0 to 24 Hours (TWA0-24hr) of Heart Rate (HR) After 14 Days of Treatment in Type 2 Diabetes Mellitus (T2DM) Participants in Part 2

  Semi-recumbent HR was measured in triplicate with at least a 1-2-minute interval between measurements at the following time points: baseline on Day 1; Day 14: predose, 2, 4, 6, 8, 12, 16, hours postdose; and prior to dosing on Day 15. The repeated measurements were averaged before conducting the analysis. TWA0-24hr was calculated as the AUC divided by the time period of over which the measurements were made (i.e. 24 hrs.). Change from baseline TWA0-24hr HR was calculated as the TWA0-24hr HR at Day 14 minus baseline where baseline was defined as predose on Day 1.

  Baseline (predose Day 1) and up to 24 hours post Day 14 dose

• Change From Baseline in Time-weighted Average From 0 to 24 Hours (TWA0-24hr) of Heart Rate (HR) After 19 Days of Treatment in Type 2 Diabetes Mellitus (T2DM) Participants in Part 2

  Semi-recumbent HR was measured in triplicate with at least a 1-2-minute interval between measurements at the following time points: baseline on Day 1; Day 19: predose, 2, 4, 6, 8, 12, 16, hours post dose; and prior to dosing on Day 20. The repeated measurements were averaged before conducting the analysis. TWA0-24hr was calculated as the AUC divided by the time period of over which the measurements were made (i.e. 24 hrs.). Change from baseline TWA0-24hr HR was calculated as the TWA0-24hr HR at Day 19 minus baseline where baseline was defined as predose on Day 1.

  Baseline (predose Day 1) and up to 24 hours post Day 19 dose

• Change From Baseline in Time-weighted Average From 0 to 24 Hours (TWA0-24hr) of Heart Rate (HR) After 24 Days of Treatment in Type 2 Diabetes Mellitus (T2DM) Participants in Part 2

  Semi-recumbent HR was measured in triplicate with at least a 1-2-minute interval between measurements at the following time points: baseline on Day 1; Day 24: predose, 2, 4, 6, 8, 12, 16, hours postdose; and prior to dosing on Day 25. The repeated measurements were averaged before conducting the analysis. TWA0-24hr was calculated as the AUC divided by the time period of over which the measurements were made (i.e. 24 hrs.). Change from baseline TWA0-24hr HR was calculated as the TWA0-24hr HR at Day 24 minus baseline where baseline was defined as predose on Day 1.

  Baseline (predose Day 1) and up to 24 hours post Day 24 dose

• Change From Baseline in Time-weighted Average From 0 to 24 Hours (TWA0-24hr) of Heart Rate (HR) After 29 Days of Treatment in Type 2 Diabetes Mellitus (T2DM) Participants in Part 2

  Semi-recumbent HR was measured in triplicate with at least a 1-2-minute interval between measurements at the following time points: baseline on Day 1; and Day 29: predose, 2, 4, 6, 8, 12, 16 and 24 hours postdose. The repeated measurements were averaged before conducting the analysis. TWA0-24hr was calculated as the AUC divided by the time period of over which the measurements were made (i.e. 24 hrs.). Change from baseline TWA0-24hr HR was calculated as the TWA0-24hr HR at Day 29 minus baseline where baseline was defined as predose on Day 1.

  Baseline (predose Day 1) and up to 24 hours post Day 29 dose

• Change From Baseline in Peak Heart Rate (PHR) at Day 7 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2

  PHR was defined as the maximum time matched baseline adjusted heart rate over 24 hours. Semi-recumbent PHR was measured in triplicate with at least a 1-2-minute interval between measurements at the following time points: baseline on Day 1; Day 7: predose, 2, 4, 6, 8, 12, and 16 hours postdose; and prior to dosing on Day 8. The repeated measurements were averaged before conducting the analysis. Change from baseline PHR was calculated as the peak heart rate at Day 7 minus baseline where baseline was defined as predose on Day 1.

  Baseline (predose Day 1) and up to 24 hours post Day 7 dose

• Change From Baseline in Peak Heart Rate (PHR) at Day 14 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2

  PHR was defined as the maximum time matched baseline adjusted heart rate over 24 hours. Semi-recumbent PHR was measured in triplicate with at least a 1-2-minute interval between measurements at the following time points: baseline on Day 1; Day 14: predose, 2, 4, 6, 8, 12, and 16 hours postdose; and prior to dosing on Day 15. The repeated measurements were averaged before conducting the analysis. Change from baseline PHR was calculated as the peak heart rate at Day 14 minus baseline where baseline was defined as predose on Day 1.

  Baseline (predose Day 1) and up to 24 hours post Day 14 dose

• Change From Baseline in Peak Heart Rate (PHR) at Day 19 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2

  PHR was defined as the maximum time matched baseline adjusted heart rate over 24 hours. Semi-recumbent PHR was measured in triplicate with at least a 1-2-minute interval between measurements at the following time points: baseline on Day 1; Day 19: predose, 2, 4, 6, 8, 12, and 16 hours postdose; and prior to dosing on Day 20. The repeated measurements were averaged before conducting the analysis. Change from baseline PHR was calculated as the peak heart rate at Day 19 minus baseline where baseline was defined as predose on Day 1.

  Baseline (predose Day 1) and up to 24 hours post Day 19 dose

• Change From Baseline in Peak Heart Rate (PHR) at Day 24 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2

  PHR was defined as the maximum time matched baseline adjusted heart rate over 24 hours. Semi-recumbent PHR was measured in triplicate with at least a 1-2-minute interval between measurements at the following time points: baseline on Day 1; Day 24: predose, 2, 4, 6, 8, 12, and 16 hours postdose; and prior to dosing on Day 25. The repeated measurements were averaged before conducting the analysis. Change from baseline PHR was calculated as the peak heart rate at Day 24 minus baseline where baseline was defined as predose on Day 1.

  Baseline (predose Day 1) and up to 24 hours post Day 24 dose

• Change From Baseline in Peak Heart Rate (PHR) at Day 29 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2

  PHR was defined as the maximum time matched baseline adjusted heart rate over 24 hours. Semi-recumbent PHR was measured in triplicate with at least a 1-2-minute interval between measurements at the following time points: baseline on Day 1; and Day 29: predose 2, 4, 6, 8, 12, 16, and 24 hours post dose. The repeated measurements were averaged before conducting the analysis. Change from baseline PHR was calculated as the peak heart rate at Day 29 minus baseline where baseline was defined as predose on Day 1.

  Baseline (predose Day 1) and up to 24 hours post Day 29 dose

• Change From Baseline in Resting Morning Heart Rate (RMHR) After the Day 7 Dose for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2

  Semi-recumbent RMHR was measured in triplicate with at least a 1-2-minute interval between measurements. The repeated measurements were averaged for each time point. Change from baseline RMHR was calculated as the RMHR 24 hours after the Day 7 dose (predose Day 8) minus baseline. Baseline was an average of 2 readings prior to dosing on Day 1.

  Baseline (predose Day 1) and Day 8 (24 hours after Day 7)

• Change From Baseline in Resting Morning Heart Rate (RMHR) After the Day 14 Dose for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2

  Semi-recumbent RMHR was measured in triplicate with at least a 1-2-minute interval between measurements. The repeated measurements were averaged for each time point. Change from baseline RMHR was calculated as the RMHR 24 hours after the Day 14 dose (predose Day 15) minus baseline. Baseline was an average of 2 readings prior to dosing on Day 1.

  Baseline (predose Day 1) and Day 15 (24 hours after Day 14)

• Change From Baseline in Resting Morning Heart Rate (RMHR) After the Day 19 Dose for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2

  Semi-recumbent RMHR was measured in triplicate with at least a 1-2-minute interval between measurements. The repeated measurements were averaged for each time point. Change from baseline RMHR was calculated as the RMHR 24 hours after the Day 19 dose (predose Day 20) minus baseline. Baseline was an average of 2 readings prior to dosing on Day 1.

  Baseline (predose Day 1) and Day 20 (24 hours after Day 19)

• Change From Baseline in Resting Morning Heart Rate (RMHR) After the Day 24 Dose for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2

  Semi-recumbent RMHR was measured in triplicate with at least a 1-2-minute interval between measurements. The repeated measurements were averaged for each time point. Change from baseline RMHR was calculated as the RMHR 24 hours after the Day 24 dose (predose Day 25) minus baseline. Baseline was an average of 2 readings prior to dosing on Day 1.

  Baseline (predose Day 1) and Day 25 (24 hours after Day 24)

• Change From Baseline in Resting Morning Heart Rate (RMHR) After the Day 29 Dose for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2

  Semi-recumbent RMHR was measured in triplicate with at least a 1-2-minute interval between measurements. The repeated measurements were averaged for each time point. Change from baseline RMHR was calculated as the RMHR 24 hours after the Day 29 dose minus baseline. Baseline was an average of 2 readings prior to dosing on Day 1.

  Baseline (predose Day 1) and Day 30 (24 hours after Day 29)

• Area Under the Concentration-time Curve From 0 to 24 Hours (AUC0-24hr) of MK-8521 on Days 1, 7, and 14 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1

  AUC0-24hr was the area under the concentration-time curve of MK-8521 from time zero to 24 hours after administration. Plasma samples were collected from predose to 24 hours postdose for determination of AUC0-24hr. Individual values were natural log-transformed and evaluated with a linear-mixed effects model containing fixed effects for treatment, day, and treatment by day interaction, and a random effect for participant. Kenward and Roger's method was used to calculate the degree of freedom for the fixed effects. AUC0-24hr is presented as geometric mean and percent coefficient of variation of geometric mean.

  Predose and 1, 2, 4, 6, 8, 10, 12, 16, and 24 hours post-dose on Days 1, 7, and 14

• Maximum Concentration (Cmax) of MK-8521 on Days 1 and 7 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1

  Cmax was the maximum observed concentration of MK-8521 in plasma after administration. Plasma samples were collected from predose to 24 hours postdose for determination of Cmax. Individual values were natural log-transformed and evaluated with a linear-mixed effects model containing fixed effects for treatment, day, and treatment by day interaction, and a random effect for participant. Kenward and Roger's method was used to calculate the degree of freedom for the fixed effects. Cmax is presented as geometric mean and percent coefficient of variation of geometric mean.

  Predose and 1, 2, 4, 6, 8, 10, 12, 16, and 24 hours post-dose on Days 1 and 7

• Maximum Concentration (Cmax) of MK-8521 on Day 14 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1

  Cmax was the maximum observed concentration of MK-8521 in plasma after administration on Day 14. Plasma samples were collected from predose to 120 hours postdose for determination of Cmax. Individual values were natural log-transformed and evaluated with a linear-mixed effects model containing fixed effects for treatment, day, and treatment by day interaction, and a random effect for participant. Kenward and Roger's method was used to calculate the degree of freedom for the fixed effects. Cmax is presented as geometric mean and percent coefficient of variation of geometric mean.

  Predose and 1, 2, 4, 6, 8, 10, 12, 16, 24, 72, 96, and 120 hours post-dose on Day 14

• Trough Concentration (Ctrough) of MK-8521 on Days 1, 7, and 14 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1

  Ctrough was the lowest observed concentration of MK-8521 in plasma. Plasma samples were collected predose on Day 2 (sampled after the Day 1 dose and prior to Day 2 dose), 7, and 14 for determination of Ctrough. Individual values were natural log-transformed and evaluated with a linear-mixed effects model containing fixed effects for treatment, day, and treatment by day interaction, and a random effect for participant. Kenward and Roger's method was used to calculate the degree of freedom for the fixed effects. Ctrough is presented as geometric mean and percent coefficient of variation of geometric mean.

  Predose on Days 2, 7, and 14

• Time to Maximum Concentration (Tmax) of MK-8521 on Days 1 and 7 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1

  Tmax was the time required to reach the maximum concentration of MK-8521 in plasma. Plasma samples were collected from predose to 24 hours postdose for determination of Tmax. Tmax is presented as median with a full range.

  Predose and 1, 2, 4, 6, 8, 10, 12, 16, and 24 hours post-dose on Days 1 and 7

• Time to Maximum Concentration (Tmax) of MK-8521 on Day 14 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1

  Tmax was the time required to reach the maximum concentration of MK-8521 in plasma. Plasma samples were collected from predose to 120 hours postdose for determination of Tmax. Tmax is presented as median with a full range.

  Predose and 1, 2, 4, 6, 8, 10, 12, 16, 24, 72, 96, and 120 hours post-dose on Day 14

• Apparent Terminal Half Life (t1/2) of MK-8521 on Days 1 and 7 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1

  t1/2 was the time required to divide the MK-8521 concentration by half after reaching pseudo-equilibrium. Plasma samples were collected from predose to 24 hours postdose for determination of t1/2. t1/2 is presented as geometric mean and percent coefficient of variation of geometric mean.

  Predose and 1, 2, 4, 6, 8, 10, 12, 16, and 24 hours post-dose on Days 1 and 7

• Apparent Terminal Half Life (t1/2) of MK-8521 on Day 14 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1

  t1/2 was the time required to divide the MK-8521 concentration by half after reaching pseudo-equilibrium. Plasma samples were collected from predose to 120 hours postdose for determination of t1/2. t1/2 was measured on Day 14 which is the longest time point for sampling for T2DM participants in Part 1. t1/2 is presented as geometric mean and percent coefficient of variation of geometric mean.

  Predose and 1, 2, 4, 6, 8, 10, 12, 16, 24, 72, 96, and 120 hours post-dose on Day 14

• Accumulation Ratio of the Area Under the Concentration-time Curve From 0 to 24 Hours (AUC0-24hr) of MK-8521 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1

  Plasma samples were collected from predose to 24 hours postdose for determination of the accumulation ratio of AUC0-24hr. The geometric mean accumulation ratio was calculated as Day 7 AUC0-24hr/Day 1 AUC0-24hr and presented as geometric mean ratio with a full range.

  Predose and 1, 2, 4, 6, 8, 10, 12, 16, and 24 hours post-dose on Days 1 and 7

• Accumulation Ratio of the Maximum Concentration (Cmax) of MK-8521 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1

  Plasma samples were collected from predose to 24 hours postdose for determination of the accumulation ratio of Cmax. The geometric mean accumulation ratio was calculated as Day 7 Cmax/Day 1 Cmax and presented as geometric mean ratio with a full range.

  Predose and 1, 2, 4, 6, 8, 10, 12, 16, and 24 hours post-dose on Days 1 and 7

• Accumulation Ratio of the Trough Concentration (Ctrough) of MK-8521 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1

  Plasma samples were collected predose on Days 2 (sampled after the Day 1 dose and prior to Day 2 dose) and 7 for determination of the accumulation ratio of Ctrough. The geometric mean accumulation ratio was calculated as Day 7 Ctrough/Day 1 Ctrough (sampled after the Day 1 dose and prior to Day 2 dose) and presented as geometric mean ratio with a full range.

  Predose on Days 2 and 7

• Area Under the Concentration-time Curve From 0 to 24 Hours (AUC0-24hr) of MK-8521 on Days 1, 7, and 14 for Type 2 Diabetes Mellitus (T2DM) and Non-Diabetic Overweight/Obese Participants in Part 2

  AUC0-24hr was the area under the concentration-time curve of MK-8521 from time zero to 24 hours after administration. Plasma samples were collected from predose to 24 hours postdose for determination of AUC0-24hr. Individual values were natural log-transformed and evaluated with a linear-mixed effects model containing fixed effects for treatment, day, and treatment by day interaction, and a random effect for participant. Kenward and Roger's method was used to calculate the degree of freedom for the fixed effects. AUC0-24hr is presented as geometric mean and percent coefficient of variation of geometric mean.

  Predose and 1, 2, 6, 10, 16, and 24 hours postdose on Days 1, 7, and 14

• Accumulation Ratio of the Area Under the Concentration-time Curve From 0 to 24 Hours (AUC0-24hr) of MK-8521 for Type 2 Diabetes Mellitus (T2DM) and Non-Diabetic Overweight/Obese Participants in Part 2

  Plasma samples were collected from predose to 24 hours postdose for determination of the accumulation ratio of AUC0-24hr. The geometric mean accumulation ratio was calculated as Day 7 AUC0-24hr/Day 1 AUC0-24hr and presented as geometric mean ratio and percent geometric coefficient of variation.

  Predose and 1, 2, 6, 10, 16, and 24 hours post-dose on Days 1 and 7

Secondary Outcomes (17)

• Change From Baseline in Fasting Plasma Glucose (FPG) at Day 7 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1

  Predose on Days 1 (baseline) and 7

• Change From Baseline in Fasting Plasma Glucose (FPG) at Day 14 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1

  Predose on Days 1 (baseline) and 14

• Change From Baseline in 24-hour Weighted Mean Glucose (WMG) at Day 7 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1

  Baseline (predose and before food on Day 1) and up to 24 hours post Day 7 dose

• Change From Baseline in 24-hour Weighted Mean Glucose (WMG) at Day 14 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1

  Baseline (predose and before food on Day 1) and up to 24 hours post Day 14 dose

• Change From Baseline in Fasting Plasma Glucose (FPG) at Day 14 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2

  Predose on Days 1 (baseline) and 14

Study Arms (8)

Part 1: MK-8521 64/120 μg/day

EXPERIMENTAL

Type 2 diabetes mellitus (T2DM) participants received once daily subcutaneous MK-8521 starting at 64 μg on Days 1 to 7 and escalated to 120 μg on Days 8 to 14.

Drug: MK-8521

Part 1: MK-8521 34/72 μg/day

EXPERIMENTAL

T2DM participants received once daily subcutaneous MK-8521 starting at 34 μg on Days 1 to 7 and escalated to 72 μg on Days 8 to 14.

Drug: MK-8521

Part 1: Liraglutide 0.6/1.2/1.8 mg/day

ACTIVE COMPARATOR

T2DM participants received once daily subcutaneous liraglutide starting at 0.6 mg on Day 1 and 2, escalated to 1.2 mg on Days 3 to 7, and escalated to 1.8 mg on Days 8 to 14.

Drug: Liraglutide

Part 1: Placebo for MK-8521

PLACEBO COMPARATOR

T2DM participants received once daily subcutaneous placebo for MK-8521 for 14 days.

Drug: Placebo

Part 2: MK-8521 64/120/180/240/300 µg/day-T2DM

EXPERIMENTAL

T2DM participants received once daily subcutaneous MK-8521 titrated to 300 µg starting at 64 µg and increasing to 120 µg on Day 8, 180 µg on Day 15, 240 µg on Day 20, and 300 µg on Day 25. The total number of dosing days was 29.

Drug: MK-8521

Part 2: Liraglutide 0.6/1.2/1.8 mg/day-T2DM

ACTIVE COMPARATOR

T2DM participants received once daily subcutaneous liraglutide titrated to 1.8 mg starting at 0.6 mg and increasing to 1.2 mg on Day 8, and 1.8 mg on Day 15. The total number of dosing days was 29.

Drug: Liraglutide

Part 2: Placebo for MK-8521-T2DM

PLACEBO COMPARATOR

T2DM participants received once daily subcutaneous placebo for MK-8521 for 29 days.

Drug: Placebo

Part 2: MK-8521 64/120 µg/day-Non-Diabetic Overweight/Obese

EXPERIMENTAL

Non-diabetic overweight/obese participants received once daily subcutaneous MK-8521 titrated to 120 µg starting at 64 µg and increasing to 120 µg on Day 8. The total number of dosing days was 14.

Drug: MK-8521

Interventions

MK-8521 DRUG

Part 1: MK-8521 34/72 μg/day; Part 1: MK-8521 64/120 μg/day; Part 2: MK-8521 64/120 µg/day-Non-Diabetic Overweight/Obese; Part 2: MK-8521 64/120/180/240/300 µg/day-T2DM

Liraglutide DRUG

Part 1: Liraglutide 0.6/1.2/1.8 mg/day; Part 2: Liraglutide 0.6/1.2/1.8 mg/day-T2DM

Placebo DRUG

Part 1: Placebo for MK-8521; Part 2: Placebo for MK-8521-T2DM

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male, or female of non-childbearing potential with Type 2 diabetes mellitus (Parts 1 and 2) or non-diabetic (Part 2)
• Body mass index (BMI) between: ≥27 and ≤40 kg/m\^2
• A1C (average blood sugar for the past 2 to 3 months) value ≥7.0 and ≤11.0 % (Part 1) or ≥ 6.5 and ≤11.0 % (Part 2) at the time of screening (T2DM participants)
• A1C value \<5.7 at the time of screening (non-diabetic subjects in Part 2 only)
• On a stable dose of metformin (≥1000 mg total daily dose) for at least 12 weeks at the time of screening (T2DM participants)

You may not qualify if:

• Mentally or legally incapacitated
• History of clinically significant psychiatric disorder of the last 5 years. Participants with situational depression may be enrolled in the trial at the discretion of the Investigator
• History of Type 1 diabetes mellitus or a history of ketoacidosis
• History of clinically significant gastrointestinal, hematological, hepatic, immunological, renal, respiratory, genitourinary or major neurological abnormalities or diseases
• History of cardiovascular disease or cardiac conduction disorder
• History of cancer (malignancy). Exceptions may include adequately treated non-melanomatous skin carcinoma or carcinoma in situ of the cervix or other malignancies which have been successfully treated ≥10 years prior to the pre-screening visit
• History of proliferative diabetic retinopathy or maculopathy
• Clinically significant diabetic autonomic neuropathy
• QTc interval ≥470 msec (for males) or ≥480 msec (for females)
• Clinical significant electrocardiogram (ECG) abnormality
• Positive for hepatitis B surface antigen, hepatitis C antibodies, or human immunodeficiency virus (HIV)
• On a weight loss program and is not weight-stable (weight stable is defined history of \<5% change in body weight in the last 3 months
• On a weight loss medication or has undergone bariatric surgery
• Major surgery, donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks prior to the pretrial (screening) visit
• Participated in another investigational trial within 4 weeks prior to the pretrial (screening) visit

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

MeSH Terms

Conditions

Diabetes Mellitus

Interventions

Liraglutide

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptide 1; Glucagon-Like Peptides; Proglucagon; Gastrointestinal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

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: November 6, 2013
• First Posted: November 13, 2013
• Study Start: November 7, 2013
• Primary Completion: October 3, 2014
• Study Completion: October 3, 2014
• Last Updated: March 8, 2022
• Results First Posted: March 8, 2022

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will share